KR100790653B1 - 유전자와 단백질들, 및 그들의 사용 - Google Patents
유전자와 단백질들, 및 그들의 사용 Download PDFInfo
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- KR100790653B1 KR100790653B1 KR1020017007911A KR20017007911A KR100790653B1 KR 100790653 B1 KR100790653 B1 KR 100790653B1 KR 1020017007911 A KR1020017007911 A KR 1020017007911A KR 20017007911 A KR20017007911 A KR 20017007911A KR 100790653 B1 KR100790653 B1 KR 100790653B1
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Abstract
본 발명에 따라, 일련의 유전자들을 B군 스트렙토코커스에서 확인하였고, 그 생성물은 유기체의 외부 표면과 결합할 수 있다. 유전자들, 또는 그들의 작용단편들은, 예를 들면 미생물 감염에 대해 환자를 면역하는 백신과 같은 치료제의 제조에 유용할 것이다.
Description
본 발명은 세균성 유전자 및 단백질의 확인 및 그들의 사용에 관한 것이다. 더욱 특별하게는, 본 발명은 면역화용 치료법 및 약품 선별에서의 그들의 사용에 관한 것이다.
Streptococcus agalactiae로도 알려져 있는, B군 스트렙토코커스(GBS)는 다양한 조건의 원인제이다. 특히, GBS는 다음을 일으킨다:
초기 발증 신생아 감염(Early onset neonatal infection)
이 감염은 보통 자궁내에서 시작되며 유아의 심한 패혈증 및 폐염을 일으키며, 이것은 치료하지 않으면 치명적이며 치료한다고 해도 10 내지 20 %의 사망률을 갖는다.
말기 발증 신생아 감염(Late onset neonatal infection)
이 감염은 탄생 직후부터 약 3개월까지의 기간에 발생한다. 이것은 폐혈증을 일으키며, 환자의 약 90 %는 합병증으로 수막염이 발생한다. 골수염, 패혈성관절염, 농양 및 내안구염을 포함한 기타의 병소(focal) 감염이 또한 발생한다.
성인 감염
이 감염은 일반적으로 점점 더 증가하는 것으로 생각되며, 출산직후의 산모, 노인층 및 면역저항성 감약자들에게 가장 빈번하게 일어난다. 이 감염은 패혈증 및 골수염, 패혈성관절염, 농양 및 내안구염을 포함한 병소감염으로 특징된다.
요로감염
GBS는 요로감염의 원인이며 임신 중의 모든 감염의 약 10 %의 원인이 된다.
수의 감염
GBS는 젖소의 만성 유선염을 일으킨다. 이것은 우유 생산을 감소시키고 따라서 경제적으로 상당히 중요한 것이다.
GBS는 항생물질로 치료할 수 있다. 그러나, 면역화가 바람직하다. 그러므로, 치료상 효과적인 백신에 사용될 수 있는 임뮤노겐을 개발하는 것이 필요하다.
본 발명은 GBS, 및 관련 유기체의 유전자 일련의 유전자들의 동정에 기초로 하며, 그것들의 생성물은 유기체의 외표면과 연관될 것이고, 따라서 면역치료법의 표적으로 유용할 수 있다.
본 발명의 한 면에 따르면, 펩티드는 B군 스트렙토코커스로부터 얻을 수 있는 pho1-13, pho3-21, pho2-15, pho3-18, pho3-22, pho3-3, pho3-17, pho2-2, pho1-5, pho3-1, pho3-23, pho3-50, pho1-14, pho2-10, pho3-14, pho3-24 및 pho3-29로 확인된 유전자중 어느 것, 또는 그들의 상동체 또는 기능성 단편을 포함하는 오페론에 의해 코드화 된다. 이와 같은 펩티드는 예를 들면, 단리되었을 때 치료용으로 적당하다.
본 발명에서 "기능성 단편"이라는 용어는 전체 유전자 또는 펩티드의 활성을 보유하는 유전자 또는 펩티드의 일부를 정의하기 위해 사용된다. 예를 들면, 펩티드의 기능성 단편은 백신 또는 항체 생산에 유용한 항원결정기로서 사용될 수 있다.
유전자 단편은 활성 펩티드를 코드화하는데 사용할 수 있다. 선택적으로, 유전자 단편은, 치료효과를 발휘하기 위해 생체내의 야생형 유전자를 표적화하는,유전자 요법에 유용할 수 있다.
본 발명에 따른 펩티드는 본 발명에서 서열 ID 번호 2, 4, 6, 8, 10, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33 및 35로 확인된 아미노산 서열 또는 그들의 기능성 단편 중 어느 것을 포함할 수 있다.
세포외 또는 세포 표면 위치 때문에, 본 발명의 펩티드는 GBS에 대한 치료학적으로-효과적인 백신제조를 위한 적당한 후보일 것이다. "치료학적으로-효과적" 이란 용어는 백신의 예방효과를 포함하는 의도이다. 예를 들면, 백신은 본 발명에 따른 펩티드 또는 감염 치료를 위한 펩티드의 발현 수단을 포함할 수 있다. 백신은 GBS에 의한 감염에 대해 산모와 신생아를 보호하기 위해 임신 전 또는 임신 중 여성에게 투여될 수 있다.
본 발명의 다른 면에 따르면, 펩티드 또는 유전자들은 잠재적인 항균제의 선별 또는 독성(virulence)의 검출에 사용될 수 있다.
본 발명의 또 다른 면은 본 발명에서 동정된 생성물을 B군 스트렙토코커스 균주에 의한 감염과 관련된 상태의 치료 또는 예방에 사용하는 것이다.
비록 단백질을 환자의 치료에 사용하는 것으로 설명하였지만, 본 발명의 생 성물을 수의적으로 사용하는 것도 본 발명의 범위 내에서 고려된다. 특히, 펩티드 또는 백신은 젖소의 만성 유선염 치료에 사용될 수 있다.
본 발명은 B군 스트렙토코커스(Group B Steptococci: GBS) 균주 M732에 관하여 설명한다. 그러나, 모든 GBS 균주들 및 많은 기타 세균성 균주들은 관련 펩티드 또는 M732의 펩티드와 아미노산 서열 상동성을 갖는 관련 펩티드 또는 단백질을 포함할 수 있다. 펩티드를 함유할 수 있는 유기체는, S. pneumoniae, S. pyogenes, S. suis, S. milleri, C 및 G군 Streptococci 및 Enterococci를 포함하지만, 이것으로 한정되는 것은 아니다. 이들 각각에 대한 백신은 GBS에 대해 기재한 것과 동일한 방법으로 개발될 수 있다.
바람직하게는, 백신제조에 유용한 펩티드는 본 발명에서 확인된 펩티드와의 40 %를 넘는 서열 상사성(similarity)을 갖는 것이다. 더욱 바람직하게는, 펩티드는60 %를 넘는 서열 상사성을 갖는다. 가장 바람직하게, 펩티드는 80 %를 넘는 서열 상사성, 예를 들면 95 %의 상사성을 갖는다.
본 발명에 따른 유전자를 특성화함으로써, 기타 미생물에서 상동성을 수립하는데 유전자 서열을 사용하는 것이 가능하다. 이 방법으로, 기타 미생물이 유사한 외표면 생성물들을 갖는가를 결정하는 것이 가능하다. 서열 상동성은 예를 들면 EMBL 또는 Genbank와 같은 존재하는 데이타베이스에서 조사함으로써 수립될 수 있다.
본 발명에 따른 펩티드들 또는 단백질들은 공지의 방법으로 정제되고 단리될 수 있다. 특히, 유전자 서열을 확인함으로써, 적당한 숙주에서 유전자를 발현시키는 재조합술을 사용하는 것이 가능할 것이다. 활성 단편들 및 상동체들은 동정될 수 있으며 치료법에 유용할 것이다. 예를 들면, 펩티드들 또는 그들의 활성 단편들은 면역 반응을 얻기 위해, 백신 중 항원결정기로서 사용될 수 있다. 이들은 또한 수동면역, 또는 진단적 응용을 위한 항체들의 제조에 사용될 수 있다. 적당한 항체는 모노크로날 항체들, 또는 단일 사슬 fv 단편을 포함한 그들의 단편을 포함한다. 항체 제조방법은 당업자들에게는 명백할 것이다.
감쇠된(attenuated) 미생물을 기초로 한 백신 제조는 당업자들에게 알려져 있다. 백신 조성물들은 필요 또는 요구에 따라, 예를 들면 명반과 같은 적당한 담체 또는 보조제와 제제화될 수 있고, B군 스트렙토코커스(streptococci) 또는 기타 관련 미생물에 대한 효과적인 면역화를 제공하기 위한 치료법에 사용될 수 있다. 백신 제제의 제조는 당업자에게는 명백할 것이다.
더욱 일반적으로, 및 당업자들에게 잘 알려진 바와 같이, 본 발명의 활성 성분의 적당한 양은 치료 용도로서 적당한 담체 또는 부형제에 따라, 및 투여 경로에 따라 선택될 수 있다. 이들 인자는 치료될 상태의 성질/심각성, 대상자의 유형 또는 건강등과 같은 알려진 기준들에 따라 선택 또는 결정될 수 있다.
본 발명의 제품은 다음과 같이 동정되었다.
GBS(균주 M732) 염색체 DNA의 부분 유전자 라이브러리를 플라즈미드 벡터 pFW-phoA1, pFW-phoA2 및 pFW-phoA3를 사용하여 제조하였다(Podbielski, A. et al. 1996. Gene 177:137-147). 이들 플라즈미드들은 성분을 이루는 스펙티노마이신 아데닐트란스퍼라제 항체물질 내성 마커를 가지며, 이들은 높은 수준의 스펙티노마이신 내성을 제공하고, 그러므로 쉽게 선택된다. 더우기, 이들 벡터는 알칼리성 포스파타제에 대한 절단형(리더가 없는) Escherichia coli phoA 유전자를 함유한다. 세개의 벡터는 상류 인프레임(inframe) BamHI 제한효소부위와 비교하여, 리더가 없는 phoA 유전자가 존재하는 판독 프레임에 대해서만 다르다. 이 절단형 E. coli
phoA 유전자는 세균막을 가로질러 이 효소를 배출하는 적당한 리더 서열이 부족하기 때문에, 이들 플라즈미드가 E.coli phoA 돌연변이체(예를 들면, 균주 DH5α)에서 증식될 때 세포외 알칼리성 포스파타제 활성이 없다. 색소생성 알칼리 포스파타제 기질, XP(5-브로모-4-클로로-3-인돌릴-포스페이트)는 완전한 세균성 세포로 들어가지 않고 그러므로 배출된 또는 표면 결합된 알칼리 포스파타제 활성만이 검출될 수 있다. 배출된 또는 표면 결합된 알칼리 포스파타제 활성이 존재하면, 색소생성 XP 기질은 쪼개져서 청색 안료를 산출하며 대응 세균집락은 그들의 청색에 의해 확인될 수 있다.
플라즈미드 DNA는 BamHI로 완전 소화(digested)되었고 쉬림프 알칼리 포스파타제를 사용하여 탈인되었다. GBS 게놈성 DNA는 Sau3AI에 의해 부분적으로 소화되었고 슈크로스 구배에서 크기로 분류되었고, 크기가 1 kb 미만인 단편을 제조된 pFW-phoA 벡터로 결찰하였다. E. coli 균주 DH5 α를, 기능적 phoA 유전자가 부족하기 때문에, 클로닝 숙주로 선택하였다. 재조합 플라즈미드를 스펙티노마이신 100 ㎍/ml와 색소생성 XP 기질 40 ㎍/ml를 함유하는 루리아 아가(Luria agar) 상에서 선택하였다. 리더없는 phoA 유전자의 배출 신호 서열을 보충하는 GBS 삽입 DNA를 함유하는 플라즈미드가 잠복되어 있는 E. coli 형질전환체를 청색 집락으로 확인하였다. 약 30000개의 다른 GBS 삽입 DNA를 함유하는 재조합 플라즈미드를 이 방법으로 선별하였고, 이후의 연구를 위해, 리더없는 phoA를 보충하는 83개의 재조합 플라즈미드를 선택하였다.
이 실험으로부터, 각각 하나의 유전자(또는 그들의 일부)를 갖는 플라즈미드를 함유하는 몇몇 클론을 선택하였고, 이들은 리더없는 phoA를 보충한다.
각 클론에서 유전자를 확인함으로써, 다음과 같이, 전장(full-length) 유전자 서열을 얻는 것이 가능하다.
확인되고 서열화된 유전자 단편을 사용하여, 게놈성 DNA 서열화를 위한 올리고뉴클레오티드 프라이머들을 설계하였다. 이들 프라이머를 얻은 서열로부터 "외부"방향으로 서열화되도록 디자인하였다. 일단 서열을 판독하면, 얻은 서열이 유전자의 5' 및 3' 말단에 도달했는지를 확인하였다. 이들 특성의 존재는 상동 서열에 대해, 5' 말단의 경우, 샤인-달가르노 공통 서열(Shine-Dalgarno consensus sequence)에 의해 선행되는 AUG 개시코돈의 존재, 및 3' 말단의 경우, 번역 종결(중지)코돈의 존재에 대해 체크하여 확인하였다.
전장 유전자를 확인한 후, 전장 생성물을 증폭하기 위해 프라이머를 설계하였다. 사용된 프라이머들은 스트렙토코커스 발현 시스템으로 생성물의 연이은 클로닝을 허용하도록 제한 효소 인식부위(5' 말단에서 NcoI 및 3' 말단에서 Ecoo019I)를 포함한다.
상기 프라이머를 사용하여 PCR을 실시하였고, 생성물을 pCR 2.1 클로닝 벡터(In Vitrogen)로 클론하였다. 클론된 단편의 존재를 확인한 후, DNA를 제한 효소 NcoI 및 Ecoo0109I를 사용하여 절개하였다.
이 단편이 삽입된 벡터는 pNZ8048의 변형된 형이었다(Kuipers, O.P. et al.(1998) J. Biotech 64:15-21). 복제의 락토코커스 기원, 클로람페니콜 내성 마커, 유도성 니신 프로모터 및 다중클로닝 부위를 장착하는 이 벡터는, NcoI 부위에 5-최말단의 측면에 접하고, 다중클로닝 부위(Eco019I 부위 포함) 중앙에서 분할된 두개의 10X His 태그, 및 His 태그의 3' 말단의 종결(중지)코돈으로 다중클로닝 부위를 대치함으로써 변경되었다.
관심있는 유전자를 10X His 태그가 코딩 영역에 대해 3' 위치에 있도록 삽입하였다. 재조합 플라즈미드를 L.lactis(균주 NZ9000 - Kuipers, O. P. et al.(1998)Supra)로 형질전환시킨 후, 액체 배양물 400 ml를 설정하고, 이 배양물에 니신을 첨가하여 단백질의 번역을 유도하였다. 2시간 동안 배양시킨 후, 세포를 수확하고 비드 비팅(bead beating)으로 세포를 용해시켰다. 생성된 용해물을 원심분리하여 청정시키고 금속 친화성 칼럼(Talon, Clonetech)을 통과시켰다. 결합된 단백질을 이미다졸로 용출시키기기 전에 칼럼을 반복하여 세척하였다.
His-태그된 재조합 단백질을 함유하는 분획을 확인하기 위해, 각 분획 유래의 분취량을 웨스턴 블롯되고 항-His 항체로 프로브된 SDS-PAGE로 분석하였다.
얻어진 재조합 단백질을 사용하여 면역화 전에 수확한 예비-면역 혈청을 갖는 뉴질랜드 흰 토끼를 면역시켰다. 면역 강화 후, 토끼들을 희생시키고 혈청을 모았다. 이 혈청을 웨스턴 블롯, ELISA 및 동물 보호 모델에 사용하였다.
동물 연구로부터 얻은 혈청을 사용하여 면역흡착 연구를 실시하였다.
B군 스트렙토코커스를 8시간 동안 20 ml 토드 헤위트 브로스(Todd Hewitt broth)(THB)에서 성장시키고, 수확하고 PBS 5 ml에 재현탁하였다. 이것의 분취량 50 ㎕를 96 웰 플레이트의 웰을 코팅하는데 사용하였다(Nunc Immuno-Sorb). 이것을 세균이 플레이트상에 흡착되도록 하기 위해 4 ℃에서 철야 방치하였다. 플레이트를 PBS로 두번 세척하고, 그 다음 37 ℃ 에서 1시간 동안 PBS 중의 3 % BSA로 차단시켰다. 다시 플레이트를 세척하였다. 혈청의 일련의 10배 희석액을 PBS 중에서 제조하고 이 희석액 50 ㎕를, 이중으로, 플레이트의 웰들에 첨가하였다. 플레이트를 덮고 1 시간동안 37 ℃에서 인큐베이트하였다. 플레이트를 세척하고, 그 다음 1:5000의 농도로 항-토끼 알칼리 포스파타제 컨쥬게이트된 2차 항체 50 ㎕를 각 웰에 첨가하였다. 37 ℃에서 1 시간 동안 인큐베이트한 후, 플레이트를 다시 세척하였다. 기질(PNPP) 50 ㎕을 각 웰에 첨가하고, 30 분 동안 반응을 진행시킨 후, 405 nm에서 흡광도를 기록하였다.
또한, 면역화된 토끼에 대한 보호 효과를 시험하기 위해 동물 보호 연구를 수행하였다.
GBS M732를 THB에서 정-대수기(mid-log phase)에 다다를 때까지 - 약 5 시간 성장시켰다. 계수 챔버에서 세포의 수를 세고, 세균을 면역전 또는 시험 혈청중 2x 107 세균/ml의 농도로 희석하였다. 이것의 50 ㎕를 생후 0-1 일의 마우스들에 복강 내 경로를 통해 주입하였다. 마우스들을 48 시간에 걸쳐 생존을 관찰하였다.
이하의 실시예들은 본 발명을 설명한다.
실시예 1
첫번째 클론은 SEQ ID NO. 2로 확인된 아미노산 서열을 갖는, 서열 ID 번호 1로 확인된 유전자 서열을 함유하였고, Pho1-13으로 분류되었다.
Pho1-13의 아미노산 서열을 비교하였다.
GBS pho1-13 유전자 생성물에 대한 동족체는 Streptococcus pyogenes, S. pneumoniae, S. salivarius, Escherichia coli, Yersinia enterocolitica, Aquifex aeolicus, Helicobacter pylori 및 Haemophilus influenzae에서 확인될 수 있다. S. pyogenes 및 S. pneumoniae 동족체를 게놈 서열 자료로부터 확인하였고 유전자 또는 유전자 생성물을 확인하는데 이용할 수 있는 주석은 없었다. 모든 다른 경우에는, 상기 동족체 ATP-의존 Clp 프로테아제 단백질 분해 구성단위로 확인될 수 있다. Clp 프로테아제의 촉매 활성은 ATP 및 마그네슘의 존재하에 단백질을 작은 펩티드로 가수분해한다(Giffard, P.M. et al. 1993. J. Gen. Microbiol. 139:913-920). 그밖에, Clp 프로테아제의 ClpP 성분은 열처리응답의 일부로서 유도된다고 보여지며(Kroh, H.E. 및 L.D. Simon. 1990. J. Bacteriol. 172:6026-6037), 이 구성단위 또는 완전 단백질분해 영역은 세균성 표면과 관련된 것으로 보인다.
상기와 같이 실시된 면역연구의 결과는 다음과 같다.
치료 | 동물의 수 | 생존 동물의 수 | |
시간(hrs) 24 48 | |||
PBS | 10 | 7 | 0 |
예비 면역 | 37 | 13 | 0 |
면역 | 38 | 17 | 9 |
실시예 2
두번째 클론을 pho1-14로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 유전자(또는 그 일부)를 함유하며 이것은 리더없는 phoA를 보충한다. 뉴클레오티드 및 유도된 아미노산 서열은 각각 서열 ID 번호 3 및 4로 나타내었다.
Pho1-14의 아미노산 서열을 비교하였다.
GBS pho1-14 유전자 생성물에 대한 동족체는 Streptococcus pyogenes,
Enterococcus faecalis 및 Streptococcus pneumoniae에서 확인될 수 있다. 이들 동족체를 게놈 서열 자료로부터 확인할 수 있었고 유전자 또는 유전자 생성물을 확인하는데 이용할 수 있는 주석은 없었다. 또한, Shigella flexneri(SpaR) 및 Yersinia pseudotuberculosis(YscT)로부터 두개의 가능한 동족체를 확인하였다. 이들 후자의 두 동족체는 세균성막에 단단히 매달려 있다고 믿어지는 단백질과 관련된다(Bergman, T. et al. 1994. J. Bacteriol. 176:2619-2626). S. flexneri에서, spaR 유전자의 생성물은 상피세포의 침입에 대해 중요하다고 보여진다(Sasakawa, C. et al. 1993. J. Bacteriol. 175:2334-2346). 그밖에, spaR 유전자의 생성물은 침입 플라즈미드 항원의 표면 태위(presentation)에도 요구된다. Y. pseudotuberculosis 중의 동족체 단백질은 Yop 분비시스템의 성분이며 이 유기체 중의 독성에 중요하다.
실시예 3
세번째 클론을 pho1-5로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 유전자(또는 그 일부)를 함유하며 이것은 리더없는 phoA를 보충하였다. 뉴클레오티드 및 유도된 아미노산 서열을 각각 서열 ID 번호 5 및 6으로 나타내었다.
Pho1-5의 아미노산 서열을 비교하였다.
GBS pho1-5 유전자 생성물에 대한 동족체는 오직 Streptococcus pyogenes 및 Staphylococcus carnosus(sceA)에서만 확인될 수 있다. S. pyogenes 동족체를 게놈 서열 자료로부터 확인하였고 유전자 또는 유전자 생성물을 확인하는데 이용할 수 있는 주석은 없었다. 더우기, S. carnosus로부터 sceA 유전자 생성물의 작용에 대해 이용할 수 있는 정보는 거의 없다. sceA 유전자 생성물은 Lactobacillus gasseri로부터의 응집촉진 단백질과 상당한 서열 상사성을 나타낸다. sceA 유전자 생성물의 분석을 기초로 하여, 이 분자는 잘 보존된 신호 서열을 함유하며 외관상 숨겨 있거나 세균 세포 표면과 연관되어 있다.
실시예 4
또 다른 클론을 pho3-3로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 핵산염 및 유도된 아미노산 서열을 각각 서열 ID 번호 7 및 8로 나타내었다.
Pho3-3의 아미노산 서열을 비교하였다.
GBS pho3-3 유전자 생성물에 대한 동족체는 Streptococcus mutans(rmiC), (cpsM) S. pneumoniae 및 S. pyogenes에서 확인될 수 있다. S. pyogenes 동족체를 게놈 서열 자료로부터 확인할 수 있었고 유전자 또는 유전자 생성물을 확인하는데 이용할 수 있는 주석은 없었다. S. pneumoniae에서, 동족체는 dTDP-4-케토-6-데옥시글루코스-3,5-에피머라제로 확인될 수 있다. 다른 두 경우에, 상기 동족체들은 dTDP-4-케토-L-람노스 리덕타제(rmlC)로 확인이능하다. S. mutants에서, 이 효소를 코드화하는 유전자는 rml 좌위의 일부이다. rml 좌위는 S. mutans 다당류 캡슐중의 람노스 성분의 중간 전구체, dTDP-람노스의 생합성에 포함되는 효소와 상당한 상사성을 나타내는 세개의 유전자로 이루어진다(Tsukikoka, Y. et al. 1997. J. Bacteriol. 179:1126-1134). 또한 S. pneumoniae에서 상사적 좌위가 확인되었다 (Coffey, T.J. et al. 1998. Mol. Micobiol. 17:73-83). 대부분의 모든 Streptococci는 특징적으로 다당류와 결합된 그들의 세포벽에 람노스를 가지며 (Schleifer, K.H. 및 R. Kilper-Balz 1987. Syst. Appl. Microbiol. 10:1-19), dTDP-4-케토-L-람노스 리덕타제가 Streptococci 중의 외표면에 결합되어 있을 가능성이 높다.
실시예 5
또 다른 클론을 pho2-10으로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다.
뉴클레오티드 서열을 서열 ID 번호 9로 나타내었다. 이것으로부터, 상류 및 하류 코딩영역을 확인하였고, 유도된 아미노산 서열을 서열ID 번호 10 및 11로 나타내었다.
Pho2-10의 아미노산 서열을 비교하였다.
GBS pho2-10 유전자 생성물에 대한 동족체를 Streptococcus pyogenes, Enterococcus faecalis, Debaryomyces occidentalis(hatI) 및 Escherichia coli(trkD)에서 확인할 수 있다. S. pyogenes 및 E. faecalis 동족체를 게놈 서열 자료로부터 확인할 수 있었고 유전자 또는 유전자 생성물을 확인하는데 이용할 수 있는 주석은 없었다. Yeast D. occidentalis에서, hak1 유전자는 E. coli의 trkD
유전자의 동족체이다(Banuelos, M.A. et al. 1995. EMBO J. 14:3021-3027). E. coli의 trkD 유전자는 kup 칼륨 흡수 시스템의 일부이다. 본 발명에서 확인된 특이 동족체는 kup 칼륨 흡수 단백질이다. kup 시스템은 E. coli 내의 구성성 칼륨 흡수 시스템이다. kup 시스템 칼륨 흡수 단백질은 막을 적어도 12배 확장시킨다고 예상되는 강한 소수성 N-말단을 함유한다. Kup는 기타 공지의 막 단백질 서열과 동족체가 아니다. 여기에는 ATP 결합이 없고, 이 시스템은 화학삼투 구배에 의해 추진된다고 예상된다(Schleyer, M. & E.P. Bakker, 1993. J. Bacteriol. 175:6925-6931).
실시예 6
또 다른 클론을 pho2-15으로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열 ID 번호 12 및 13으로 나타내었다.
Pho2-15의 아미노산 서열을 비교하였다.
GBS pho2-15 유전자 생성물에 대한 동족체를 Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis 및 Escherichia coli(gatC 및 SgcC)에서 확인할 수 있다. S. pyogenes, S.pneumoniae 및 E. faecalis 동족체를 게놈 서열 자료로부터 확인하였고, 유전자 또는 유전자 생성물을 확인하는데 이용할 수 있는 주석은 없었다. E. coli에서, gatC 및 sgcC 유전자 생성물은 포스포에놀리피루베이트-의존 슈가 포스포트란스퍼라제 시스템(PTS), 주요 탄수화물 활성-이송 시스템의 IIC 성분으로 확인될 수 있다. PTS 시스템에서, IIC 성분은 전형적으로 세포외 탄수화물의 결합을 포함하며 IID 성분과 착물을 형성하여 막 채널을 이룬다(Nobelmann, B. 및 J.W. Lengeler. 1995. Biochim. Biophys. Acta 1262:69-72)
실시예 7
또 다른 클론을 pho2-2로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 각각 서열 ID 번호 14 및 15로 나타내었다.
Pho2-2의 아미노산 서열을 비교하였다.
GBS pho2-2 유전자 생성물에 대한 동족체를 Enterococcus faecalis,
Escherichia coli(malK 및 afuC), Bacillus subtilis(gln0), Haemophilus influenzae(yebM 및 potA), Streptococcus pyogenes, Streptococcus pneumoniae 및 Salmonella typhimurium(malK)에서 확인할 수 있다. E. faecalis, S. pyogenes 및 S.pneumoniae 동족체를 게놈 서열 자료로부터 확인하였고, 유전자 또는 유전자 생성물을 확인하는데 이용할 수 있는 주석은 없었다. 모든 다른 경우에, 동족체들은 ABC형 전달제의 일부인 ATP-결합 물질수송 단백질을 나타낸다. ABC형 전달제의 많은 성분은 결합된 막 또는 세포 표면이다. 이들 시스템은 세포외 환경으로부터 세포내 구획으로의 고분자의 물질수송에 관련된다.
실시예 8
또 다른 클론을 pho3-14로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열 ID 번호 16 및 17로 나타내었다.
Pho3-14의 아미노산 서열을 비교하였고, 출판 데이타베이스 어느 것에서도 동족체가 확인되지 않았다. GBS pho3-14 유전자 생성물에 대한 하나의 동족체를 Streptococcus pyogenes에서 확인할 수 있었고 유전자 또는 유전자 생성물을 확인하는데 이용할 수 있는 주석은 없었다. 출판된 자료를 찾기 위해 S. pyogenes 동족체들을 사용하였으나 추가 정보는 없었다. Pho3-14 생성물은 리더없는 phoA를 보충하기 때문에, 이 단백질(또는 그것의 일부)이 대부분 아마도 세포외에 위치할 것이라고 결론지을 수 있다.
실시예 9
또 다른 클론을 pho3-17로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열 ID 번호 18 및 19로 나타내었다.
Pho3-17의 아미노산 서열을 비교하였다.
GBS pho3-17 유전자 생성물에 대한 하나의 동족체를 N-아세틸 뮤라미다제에 나타나는 것과 상사성을 갖는 Streptococcus mutans 및 Lactococcus lactis중에서 확인할 수 있었다. 상사성은 Bacillus subtilis로부터 미확인된 유전자 yubE에서도 나타난다.
N-아세틸뮤라미다제는 세포 분할에 관여하는 자기용혈소이다. pho3-17이 리더없는 phoA 유전자를 보충한다는 사실과 함께 제한된 이 정보를 사용하여, pho3-17 생성물은 가장 바람직하게는 세포외에 위치한다고 결론지을 수 있다.
실시예 10
또 다른 클론을 pho3-18로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열 ID 번호 20 및 21로 나타내었다.
Pho3-18의 아미노산 서열을 비교하였다.
GBS pho3-18 유전자 생성물에 대한 동족체는 Streptococcus pyogenes 및 Streptococcus pneumoniae에서 확인할 수 있다. 이들 동족체를 게놈 서열 자료로부터 확인하였고, 유전자 또는 유전자 생성물의 확인을 위해 사용할 수 있는 주석은 없었다. 출판된 자료를 찾기 위한 S. pyogenes 및 S. pneumoniae 동족체를 사용한 것은 외표면 및 막 스핀 단백질과의 상당한 상사성을 나타내었다. ORF-18 생성물이 리더없는 phoA 유전자를 보충하므로, 이 단백질( 또는 그 일부)이 세포외에 위치하 는 것이 가장 바람직하다고 결론지을 수 있다.
실시예 11
또 다른 클론을 pho3-1로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열 ID 번호 22 및 23으로 나타내었다.
Pho3-1의 아미노산 서열을 비교하였다.
GBS pho3-1 유전자 생성물에 대한 동족체는 Streptococcus pyogenes 및 Streptococcus pneumoniae, Bacillus subtillis(yutD) 및 Enterococcus faecalis에서 확인할 수 있다. S. pyogenes, S. pneumoniae, 및 E. faecalis 동족체를 게놈 서열 자료로부터 확인하였고, 유전자 또는 유전자 생성물의 확인을 위해 사용할 수 있는 주석은 없었다. B. subtilis에서, yutD 유전자 생성물의 기능은 알려지지 않았다. 그러나, yutD 유전자가 세포벽 합성에 관여하는 유전자를 함유하는 영역에서 B. subtilis 염색체에 위치한다는 것을 알 수 있다. 이 DNA 서열이 리더없는 phoA 유전자를 보충한다는 사실은 이 유전자 생성물이 세포외에 위치한다는 것을 제안한다.
실시예 12
또 다른 클론을 pho3-21로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열확인 번호 24 및 25로 나타내었다.
Pho3-21의 아미노산 서열을 비교하였다.
GBS pho3-21 유전자 생성물에 대한 동족체는 Streptococcus pyogenes, Streptococcus pneumoniae, Latobacillus fermentum(bspA) 및 Lactobacillus reuteri(cnb)에서 확인할 수 있다. S. pyogenes 및 S. pneumoniae 동족체를 게놈 서열 자료로부터 확인하였고, 유전자 또는 유전자 생성물의 확인을 위해 사용할 수 있는 주석은 없었다. L. fermentum에서, bspA 유전자 생성물은 세균성 용질-결합 단백질의 Ⅲ족과 몇몇 서열 상사성을 갖는 기본 세포 표면에 위치하는 단백질로 확인되었다(Turner, M.S. et al. 1997. J. Bacteriol. 179:3310-3316). L. reuteri에서, cnb 유전자 생성물은 세균성 ABC 전달제의 용질-결합 성분과 상당한 서열 상사성을 갖는 콜라겐 결합 단백질로 동정되었다(Roos, S. et al. 1996. FEMS Microbiol. Lett. 144:33-38).
실시예 13
또 다른 클론을 pho3-22로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열 ID 번호 26 및 27으로 나타내었다.
Pho3-22의 아미노산 서열을 비교하였다.
GBS pho3-22 유전자 생성물에 대한 동족체는 Enterococcus faecalis, Streptococcus equisimilis(lppC), Pseudomonas fluorescens(oprI) 및 Streptococcus thermophilus(orf142)에서 확인할 수 있다. E. faecalis 동족체를 게놈 서열 자료로부터 확인하였고, 유전자 또는 유전자 생성물의 확인을 위해 사용할 수 있는 주석은 없었다. S. equisimilis에서, lppC 유전자 생성물은 Haemophilus influenzae로부터 E(P4) 외부 막 단백질과 동족체인 리포프로테인으로 확인되었다(Gase, K. et al. 1997. Med. Microbiol. Immunol. 186:63-73). 그밖에, P. fluorescens oprI 유전자는 주요한 외막 리포프로테인을 코드화한다 (Cornelis, P. et al. 1989. Mol. Microbiol. 3: 421-428). S. thermophilus에서, orf142 생성물은 박테리오파지 TP-J34 및 Sfi21에 대한 수용체로서 작용할 수 있는 세포 표면이 노출된 리포프로테인으로 추정 확인되었다(Neve, H. et al. 1998. Virology 241:61-72). ORF3-22 생성물은 상기 동족체, 특히 N-말단과 양호한 상사성을 나타낸다. 이것은 아마 리더없는 phoA 유전자의 상보성에 필요한 영역이며, 그러므로 리더 서열로서 작용한다.
실시예 14
또 다른 클론을 pho3-23으로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열 ID 번호 28 및 29으로 나타내었다.
Pho3-23의 아미노산 서열을 비교하였다.
GBS pho3-23 유전자 생성물에 대한 동족체는 Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis 및 Streptococcus mutans(perM) 에서 확인할 수 있다. S. pyogenes, S. pneumoniae 및 E. faecalis 동족체를 게놈 서열 자료로부터 확인하였고, 유전자 또는 유전자 생성물의 확인을 위해 사용할 수 있는 주석은 없었다. S. mutans에서, perM 유전자 생성물은 퍼미아제로 추정에 따라 확인되었으나, 이 단백질의 작용에 대한 기타 정보는 얻을 수 없었다. PhoA3-23 코팅 영역이 리더없는 phoA 유전자를 보충한다는 것을 고려하여, pho3-17 유전자 생성물은 아마도 세포외에 위치할 것이다.
실시예 15
또 다른 클론을 pho3-24로 표시된 플라즈미드를 함유하는 것으로 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열 ID 번호 30 및 31로 나타내었다.
Pho3-24의 아미노산 서열을 비교하였다.
GBS pho3-24 유전자 생성물에 대한 동족체는 Streptococcus mutans(dltB), Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis,
Lactobacillus casei(dltB) 및 Bacillus subtilis(dltB)에서 확인할 수 있다. S. pneumoniae, S. pyogenes 및 E. faecalis 동족체를 게놈 서열 자료로부터 확인하였고, 유전자 또는 유전자 생성물의 확인을 위해 사용할 수 있는 주석은 없었다. S. mutans, L. casei 및 B. subtilis에서, dltB 유전자 생성물은 세포막을 통해 활성화된 D-알라닌의 물질수송에 관여하는 기본 막 단백질로 동정되었다. dltB 유전자 생성물은 D-알라닐-리포테이코산(D-alanyl-lipoteichoic acid)의 생합성에 관여한 다(Heaton, M.P. 및 F.C. Neuhaus. 1992. J. Bacteriol. 174:4707-4717). L. casei 및 B. subtilis에서, dltB 유전자 생성물은, 단백질 또는 그 일부가 세포의 외부로 노출되는 것을 나타내는, 적어도 9개의 막 스패닝 영역을 함유한다고 믿어진다.
실시예 16
Pho3-29로 표시된 플라즈미드를 함유하는 또 다른 클론을 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열 ID 번호 32 및 33으로 나타내었다.
Pho3-29의 아미노산 서열을 비교하였다.
GBS pho3-29 유전자 생성물에 대한 동족체는 Borrelia burgdorferi(p23 또는 ospC), Bacillus brevis(owp) 및 Pseudomonas aeruginosa(oprI)에서 확인할 수 있다. 비록, 이들 동족체가 서로 관계가 없으나, 이들은 모두 주요 외표면 단백질을 나타낸다. B. burgdorferi에서, ospC 유전자 생성물은 이 세균의 표면에서 면역 우성 항원인 23-kDa 단백질로 동정되었다(Padula, S,J. et al. 1993. Infect. Immun. 61:5097-5105). B. brevis로부터 owp 유전자 생성물은 표면층 격자에 관여하는 두개의 주요 세포벽 단백질 중 하나이다(Tsuboi, A. 1988. J. Bacteriol. 170:935-945). 최종적으로 P. aeruginosa로부터의 oprI 유전자는 주요 외부막 리포프로테인 전구체를 코드화한다(Saint-Onge, A. et al. 1992. J. Gen. Micirobiol. 138:733-741).
실시예 17
Pho3-50으로 표시된 플라즈미드를 함유하는 또 다른 클론을 선택하였다. 이 플라즈미드는 리더없는 phoA를 보충하는 유전자(또는 그 일부)를 함유하였다. 상기 유전자의 뉴클레오티드 및 유도된 아미노산 서열을 서열 ID 번호 34 및 35로 나타내었다.
Pho3-50의 아미노산 서열을 비교하였다.
GBS pho3-50 유전자 생성물에 대한 동족체는 다양한 Streptococci(penA, pbp2B, pbpB2), Borrelia burgdorferi(pbp2), Enterococcus faecalis(pbpC), Staphylococcus aureus(pbpA), Mycobacterium leprae(pbpB) 및 Helicobacter pylori(pbp2)에서 확인될 수 있다. 모든 경우에, 상기 동족체들은 페니실린 결합 단백질(PBPs)로 동정될 수 있다. 페니실린 결합 단백질을 코드화하는 유전자들은 종종 세포벽 합성과 관련된 유전자의 클러스터에 위치한다(Pucci, M.J. et al. 1997. J. Bacteriol. 179:5632-5635). 그 밖에, PBPs는 세균 외표면에 노출되어 있는 단백질의 몇몇 또는 전체와 세균의 세포벽으로 통합된다.
SEQUENCE LISTING
<110> Microscience Limited
<120> GENES AND PROTEINS, AND THEIR USE
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atg atc cca gta gta atc gaa caa aca agt cgt ggt gaa cgt tct tat 48
Met Ile Pro Val Val Ile Glu Gln Thr Ser Arg Gly Glu Arg Ser Tyr
1 5 10 15
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Asp Ile Tyr Ser Arg Leu Leu Lys Asp Arg Ile Ile Met Leu Thr Gly
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Leu Asp Ala Gln Asp Asn Thr Lys Asp Ile Tyr Leu Tyr Val Asn Thr
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cca ggt ggt tca gta tcg gct gga ctt gct att gtg gac acc atg aac 240
Pro Gly Gly Ser Val Ser Ala Gly Leu Ala Ile Val Asp Thr Met Asn
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ttc att aaa tcg gac gta cag acg att gtt atg ggg atg gct gct tcg 288
Phe Ile Lys Ser Asp Val Gln Thr Ile Val Met Gly Met Ala Ala Ser
85 90 95
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Met Gly Thr Ile Ile Ala Ser Ser Gly Ala Lys Gly Lys Arg Phe Met
100 105 110
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Gly Gly Thr Gln Gln Ser Asp Met Ala Ile Ala Ala Glu His Leu Leu
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Lys Thr Arg His Thr Leu Glu Lys Ile Leu Ala Asp Asn Ser Gly Gln
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Ser Ile Glu Lys Val His Asp Asp Ala Glu Arg Asp Arg Trp Met Ser
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Ala Gln Glu Thr Leu Asp Tyr Gly Phe Ile Asp Glu Ile Met Ala Asn
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Gly Gly Thr Gln Gln Ser Asp Met Ala Ile Ala Ala Glu His Leu Leu
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Ser Ile Glu Lys Val His Asp Asp Ala Glu Arg Asp Arg Trp Met Ser
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Ala Gln Glu Thr Leu Asp Tyr Gly Phe Ile Asp Glu Ile Met Ala Asn
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atc aga gca tat tct ggt cct ctt tcg gtt ttc ctg cca cgt ttt aaa 48
Ile Arg Ala Tyr Ser Gly Pro Leu Ser Val Phe Leu Pro Arg Phe Lys
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Ala Cys Asp Ile Ile Val Asn Val Arg Arg Thr Ile Met Leu Phe Lys
20 25 30
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Glu Lys Ile Pro Gly Leu Ile Leu Cys Phe Ile Ile Ala Ile Pro Ser
35 40 45
tgg ttg ctt ggg ctt tat ctc cct tta ata gga gca cca gtc ttt gct 192
Trp Leu Leu Gly Leu Tyr Leu Pro Leu Ile Gly Ala Pro Val Phe Ala
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20 25 30
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Ile Leu Ile Gly Ile Ile Val Gly
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Met Asn Lys Arg Arg Lys Leu Ser Lys Leu Asn Val Lys Lys Gln His
1 5 10 15
tta gct tat gga gct atc act tta gta gcc ctt ttt tca tgt att ttg 96
Leu Ala Tyr Gly Ala Ile Thr Leu Val Ala Leu Phe Ser Cys Ile Leu
20 25 30
gct gta acg gtc atc ttt aaa agt tca caa gtt act act gaa tct ttg 144
Ala Val Thr Val Ile Phe Lys Ser Ser Gln Val Thr Thr Glu Ser Leu
35 40 45
tca aaa gca gat aaa gtt cgc gta gcc aaa aaa tca aaa atg act aag 192
Ser Lys Ala Asp Lys Val Arg Val Ala Lys Lys Ser Lys Met Thr Lys
50 55 60
gcg aca tct aaa tca aaa gta gaa gat gta aaa cag gct cca aaa cct 240
Ala Thr Ser Lys Ser Lys Val Glu Asp Val Lys Gln Ala Pro Lys Pro
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Ser Gln Ala Ser Asn Glu Ala Pro Lys Ser Ser Ser Gln Ser Thr Glu
85 90 95
gct aat tct cag caa caa gtt act gcg agt gaa gag acg gct gta gaa 336
Ala Asn Ser Gln Gln Gln Val Thr Ala Ser Glu Glu Thr Ala Val Glu
100 105 110
caa gca gtt gta aca gaa ata ccc ctg cta cca gtc agg cac aac aac 384
Gln Ala Val Val Thr Glu Ile Pro Leu Leu Pro Val Arg His Asn Asn
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130 135 140
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145 150 155 160
gct gct gca gca caa atg gct gct gca aca gga gtc cct cag tct act 528
Ala Ala Ala Ala Gln Met Ala Ala Ala Thr Gly Val Pro Gln Ser Thr
165 170 175
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Trp Glu His Ile Ile Ala Arg Glu Ser Asn Gly Asn Pro Asn Val Ala
180 185 190
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Asn Ala Ser Gly Ala Ser Gly Leu Phe Gln Thr Met Pro Gly Trp Gly
195 200 205
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Ser Thr Ala Thr Val Gln Asp Gln Val Ile Gln Leu Leu Lys Leu Ile
210 215 220
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Arg Ala Gln Gly Leu Ser Ala Gly Tyr Gln
225 230 235
<210> 6
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Met Asn Lys Arg Arg Lys Leu Ser Lys Leu Asn Val Lys Lys Gln His
1 5 10 15
Leu Ala Tyr Gly Ala Ile Thr Leu Val Ala Leu Phe Ser Cys Ile Leu
20 25 30
Ala Val Thr Val Ile Phe Lys Ser Ser Gln Val Thr Thr Glu Ser Leu
35 40 45
Ser Lys Ala Asp Lys Val Arg Val Ala Lys Lys Ser Lys Met Thr Lys
50 55 60
Ala Thr Ser Lys Ser Lys Val Glu Asp Val Lys Gln Ala Pro Lys Pro
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Ser Gln Ala Ser Asn Glu Ala Pro Lys Ser Ser Ser Gln Ser Thr Glu
85 90 95
Ala Asn Ser Gln Gln Gln Val Thr Ala Ser Glu Glu Thr Ala Val Glu
100 105 110
Gln Ala Val Val Thr Glu Ile Pro Leu Leu Pro Val Arg His Asn Asn
115 120 125
Leu Tyr Ala Val Thr Glu Thr Pro Tyr Asn Pro Ala Gln Pro Pro Asp
130 135 140
Gln Val Ala Arg Tyr Glu Gln Trp Lys Tyr Cys Gln Ala Val Gly Ser
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Ala Ala Ala Ala Gln Met Ala Ala Ala Thr Gly Val Pro Gln Ser Thr
165 170 175
Trp Glu His Ile Ile Ala Arg Glu Ser Asn Gly Asn Pro Asn Val Ala
180 185 190
Asn Ala Ser Gly Ala Ser Gly Leu Phe Gln Thr Met Pro Gly Trp Gly
195 200 205
Ser Thr Ala Thr Val Gln Asp Gln Val Ile Gln Leu Leu Lys Leu Ile
210 215 220
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225 230
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Met Thr Glu Pro Phe Phe Asp Lys Glu Leu Thr Cys Arg Pro Ile Glu
1 5 10 15
gcc att cct gaa ttg ttg gaa ttc gat att acc gtt cgt gga gac aac 96
Ala Ile Pro Glu Leu Leu Glu Phe Asp Ile Thr Val Arg Gly Asp Asn
20 25 30
cgt gga tgg ttc aaa gag aac ttt caa aaa gaa aaa atg ata ccg ctt 144
Arg Gly Trp Phe Lys Glu Asn Phe Gln Lys Glu Lys Met Ile Pro Leu
35 40 45
ggt ttc cca gaa agc ttc ttt gag gca gac aaa cta caa aat aat att 192
Gly Phe Pro Glu Ser Phe Phe Glu Ala Asp Lys Leu Gln Asn Asn Ile
50 55 60
tcg ttt aca aaa aaa aat act ttg cga ggt ctc cat gca gag cct tgg 240
Ser Phe Thr Lys Lys Asn Thr Leu Arg Gly Leu His Ala Glu Pro Trp
65 70 75 80
gat aaa tat gtt tcg atc gct gat gaa gga cgt gtg atc ggt act tgg 288
Asp Lys Tyr Val Ser Ile Ala Asp Glu Gly Arg Val Ile Gly Thr Trp
85 90 95
gtt gac ctc cgt gaa ggt gac agt ttt ggt aac gtt tac caa acg att 336
Val Asp Leu Arg Glu Gly Asp Ser Phe Gly Asn Val Tyr Gln Thr Ile
100 105 110
atc gat gcc tca aaa ggt att ttt gtt cca cgc ggc gtt gct aat ggt 384
Ile Asp Ala Ser Lys Gly Ile Phe Val Pro Arg Gly Val Ala Asn Gly
115 120 125
ttc caa gtt ctt tca gat aaa gca gct tat act tat ctc gtt aac gat 432
Phe Gln Val Leu Ser Asp Lys Ala Ala Tyr Thr Tyr Leu Val Asn Asp
130 135 140
tat tgg gca ctt gaa ctc aaa cca aaa tat gct ttc gtt aac tat gca 480
Tyr Trp Ala Leu Glu Leu Lys Pro Lys Tyr Ala Phe Val Asn Tyr Ala
145 150 155 160
gat cca aat cta ggc att cag tgg gaa aat ctw gaa gaa gca gaa gtc 528
Asp Pro Asn Leu Gly Ile Gln Trp Glu Asn Xaa Glu Glu Ala Glu Val
165 170 175
tca gaa gca gat aag aat cac cca ctt ctc aaa gat gta aaa cct ttg 576
Ser Glu Ala Asp Lys Asn His Pro Leu Leu Lys Asp Val Lys Pro Leu
180 185 190
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Lys Lys Glu Asp Leu
195
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Met Thr Glu Pro Phe Phe Asp Lys Glu Leu Thr Cys Arg Pro Ile Glu
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Ala Ile Pro Glu Leu Leu Glu Phe Asp Ile Thr Val Arg Gly Asp Asn
20 25 30
Arg Gly Trp Phe Lys Glu Asn Phe Gln Lys Glu Lys Met Ile Pro Leu
35 40 45
Gly Phe Pro Glu Ser Phe Phe Glu Ala Asp Lys Leu Gln Asn Asn Ile
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Ser Phe Thr Lys Lys Asn Thr Leu Arg Gly Leu His Ala Glu Pro Trp
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Asp Lys Tyr Val Ser Ile Ala Asp Glu Gly Arg Val Ile Gly Thr Trp
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Val Asp Leu Arg Glu Gly Asp Ser Phe Gly Asn Val Tyr Gln Thr Ile
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Ile Asp Ala Ser Lys Gly Ile Phe Val Pro Arg Gly Val Ala Asn Gly
115 120 125
Phe Gln Val Leu Ser Asp Lys Ala Ala Tyr Thr Tyr Leu Val Asn Asp
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Tyr Trp Ala Leu Glu Leu Lys Pro Lys Tyr Ala Phe Val Asn Tyr Ala
145 150 155 160
Asp Pro Asn Leu Gly Ile Gln Trp Glu Asn Xaa Glu Glu Ala Glu Val
165 170 175
Ser Glu Ala Asp Lys Asn His Pro Leu Leu Lys Asp Val Lys Pro Leu
180 185 190
Lys Lys Glu Asp Leu
195
<210> 9
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<220>
<221> CDS
<222> (1)..(570)
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<221> CDS
<222> (679)..(945)
<400> 9
tat tat tta atc gga ggg ttg gca gaa atg caa cat gtc aat cat tct 48
Tyr Tyr Leu Ile Gly Gly Leu Ala Glu Met Gln His Val Asn His Ser
1 5 10 15
tct ttt gat aaa gca tca aaa gca gga ttt att att gct tta ggc att 96
Ser Phe Asp Lys Ala Ser Lys Ala Gly Phe Ile Ile Ala Leu Gly Ile
20 25 30
gtt tat gga gat att ggt aca agc cca ctc tat acg atg caa tca ttg 144
Val Tyr Gly Asp Ile Gly Thr Ser Pro Leu Tyr Thr Met Gln Ser Leu
35 40 45
gtt gaa aac caa ggt ggt att tct agt gtc aca gaa tcg ttt atc tta 192
Val Glu Asn Gln Gly Gly Ile Ser Ser Val Thr Glu Ser Phe Ile Leu
50 55 60
ggt tct ata tct tta atc ata tgg acc ttg aca ctt att aca act atc 240
Gly Ser Ile Ser Leu Ile Ile Trp Thr Leu Thr Leu Ile Thr Thr Ile
65 70 75 80
aag tat gtg ctt gta gct tta aag gcg gat aat cac cac gaa ggt ggt 288
Lys Tyr Val Leu Val Ala Leu Lys Ala Asp Asn His His Glu Gly Gly
85 90 95
att ttt tct tta tat acc ctt gtt aga aaa atg aca cct tgg tta att 336
Ile Phe Ser Leu Tyr Thr Leu Val Arg Lys Met Thr Pro Trp Leu Ile
100 105 110
gtt ccg gct gtt att gga ggt gca acc ttg ttg tca gat gga gct ttg 384
Val Pro Ala Val Ile Gly Gly Ala Thr Leu Leu Ser Asp Gly Ala Leu
115 120 125
acg cca gct gta acc gta ctt cag ccg tta agg att aaa gta gtt cct 432
Thr Pro Ala Val Thr Val Leu Gln Pro Leu Arg Ile Lys Val Val Pro
130 135 140
agt ttg cag cat att tcc aga atc aga gta tgt tat ttt gcg acc ttg 480
Ser Leu Gln His Ile Ser Arg Ile Arg Val Cys Tyr Phe Ala Thr Leu
145 150 155 160
tta ttt act gtt act ttt gcc atc caa ggt ttg gaa cgg gtg tta ttg 528
Leu Phe Thr Val Thr Phe Ala Ile Gln Gly Leu Glu Arg Val Leu Leu
165 170 175
gaa tta ttg gcc att atg tta tat ggt ttg cct ttt ggt tta 570
Glu Leu Leu Ala Ile Met Leu Tyr Gly Leu Pro Phe Gly Leu
180 185 190
ncggtctcct tatagttttg cccatccaga agttttcaag cattaatcca tactacggtt 630
tgaaattgtt atttagtcca gagaatcata aaggtatttt tattttag gat cta ttt 687
Asp Leu Phe
tcc tgg cga caa acg gga gca gaa gca cta tac tct gac tta ggt cat 735
Ser Trp Arg Gln Thr Gly Ala Glu Ala Leu Tyr Ser Asp Leu Gly His
195 200 205
gtt ggg cgt gga aat ata cat gtt tca tgg ccg ttc gtt aag gtt gcc 783
Val Gly Arg Gly Asn Ile His Val Ser Trp Pro Phe Val Lys Val Ala
210 215 220 225
att ata ctt tct tat tgt ggg caa ggg gca tgg att tta gct aat aag 831
Ile Ile Leu Ser Tyr Cys Gly Gln Gly Ala Trp Ile Leu Ala Asn Lys
230 235 240
aac gca gga aat gaa ttg aat ccc ttt ttt gct agt att cct tcg caa 879
Asn Ala Gly Asn Glu Leu Asn Pro Phe Phe Ala Ser Ile Pro Ser Gln
245 250 255
ttt aca atg cat gtc gtt att tta gct act ttg gca gct atc atc gct 927
Phe Thr Met His Val Val Ile Leu Ala Thr Leu Ala Ala Ile Ile Ala
260 265 270
tca cag gca ctg att tct ggatcaattt accttaagtt ctgagctatg 975
Ser Gln Ala Leu Ile Ser
275
cgactaaaaa tattcccaca atttcgttca acttatcctg ttgacaatat tgggtcaaac 1035
ctacatacct ggtattaatt ggttcttatt tgccattaca acctctattg gtttgctttt 1095
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gacaactatt ttactgtctt tctttttaat tcaaaaagga gtaaagagag gttttagcta 1215
tt 1217
<210> 10
<211> 190
<212> PRT
<213> group B streptococcus
<400> 10
Tyr Tyr Leu Ile Gly Gly Leu Ala Glu Met Gln His Val Asn His Ser
1 5 10 15
Ser Phe Asp Lys Ala Ser Lys Ala Gly Phe Ile Ile Ala Leu Gly Ile
20 25 30
Val Tyr Gly Asp Ile Gly Thr Ser Pro Leu Tyr Thr Met Gln Ser Leu
35 40 45
Val Glu Asn Gln Gly Gly Ile Ser Ser Val Thr Glu Ser Phe Ile Leu
50 55 60
Gly Ser Ile Ser Leu Ile Ile Trp Thr Leu Thr Leu Ile Thr Thr Ile
65 70 75 80
Lys Tyr Val Leu Val Ala Leu Lys Ala Asp Asn His His Glu Gly Gly
85 90 95
Ile Phe Ser Leu Tyr Thr Leu Val Arg Lys Met Thr Pro Trp Leu Ile
100 105 110
Val Pro Ala Val Ile Gly Gly Ala Thr Leu Leu Ser Asp Gly Ala Leu
115 120 125
Thr Pro Ala Val Thr Val Leu Gln Pro Leu Arg Ile Lys Val Val Pro
130 135 140
Ser Leu Gln His Ile Ser Arg Ile Arg Val Cys Tyr Phe Ala Thr Leu
145 150 155 160
Leu Phe Thr Val Thr Phe Ala Ile Gln Gly Leu Glu Arg Val Leu Leu
165 170 175
Glu Leu Leu Ala Ile Met Leu Tyr Gly Leu Pro Phe Gly Leu
180 185 190
<210> 11
<211> 89
<212> PRT
<213> group B streptococcus
<400> 11
Asp Leu Phe Ser Trp Arg Gln Thr Gly Ala Glu Ala Leu Tyr Ser Asp
1 5 10 15
Leu Gly His Val Gly Arg Gly Asn Ile His Val Ser Trp Pro Phe Val
20 25 30
Lys Val Ala Ile Ile Leu Ser Tyr Cys Gly Gln Gly Ala Trp Ile Leu
35 40 45
Ala Asn Lys Asn Ala Gly Asn Glu Leu Asn Pro Phe Phe Ala Ser Ile
50 55 60
Pro Ser Gln Phe Thr Met His Val Val Ile Leu Ala Thr Leu Ala Ala
65 70 75 80
Ile Ile Ala Ser Gln Ala Leu Ile Ser
85
<210> 12
<211> 378
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(378)
<400> 12
atg cag gta ttt tta aat att gtc aat aaa ttc ttt gat cca gtt att 48
Met Gln Val Phe Leu Asn Ile Val Asn Lys Phe Phe Asp Pro Val Ile
1 5 10 15
cat atg ggt tcg gga gtt gtg atg cta att gtc atg aca ggt tta gcc 96
His Met Gly Ser Gly Val Val Met Leu Ile Val Met Thr Gly Leu Ala
20 25 30
atg ata ttt gga gtg aag ttt tct aaa gca ctt gaa ggt ggt att aag 144
Met Ile Phe Gly Val Lys Phe Ser Lys Ala Leu Glu Gly Gly Ile Lys
35 40 45
tta gct att gct ctt acg ggt att ggt gct att att ggt att tta act 192
Leu Ala Ile Ala Leu Thr Gly Ile Gly Ala Ile Ile Gly Ile Leu Thr
50 55 60
ggt gct ttt tcc gaa tca ctt caa gct ttt gtt aaa aat aca gga atc 240
Gly Ala Phe Ser Glu Ser Leu Gln Ala Phe Val Lys Asn Thr Gly Ile
65 70 75 80
aat cta agc att att gac gtt ggt tgg gct cca tta gca act att aca 288
Asn Leu Ser Ile Ile Asp Val Gly Trp Ala Pro Leu Ala Thr Ile Thr
85 90 95
tgg gga tca cca tat acg ctt tac ttc tta tta atc atg ctt att gtc 336
Trp Gly Ser Pro Tyr Thr Leu Tyr Phe Leu Leu Ile Met Leu Ile Val
100 105 110
aat att gtt atg att gtt atg aaa aaa aaa cgg ata cct tag 378
Asn Ile Val Met Ile Val Met Lys Lys Lys Arg Ile Pro
115 120 125
<210> 13
<211> 125
<212> PRT
<213> group B streptococcus
<400> 13
Met Gln Val Phe Leu Asn Ile Val Asn Lys Phe Phe Asp Pro Val Ile
1 5 10 15
His Met Gly Ser Gly Val Val Met Leu Ile Val Met Thr Gly Leu Ala
20 25 30
Met Ile Phe Gly Val Lys Phe Ser Lys Ala Leu Glu Gly Gly Ile Lys
35 40 45
Leu Ala Ile Ala Leu Thr Gly Ile Gly Ala Ile Ile Gly Ile Leu Thr
50 55 60
Gly Ala Phe Ser Glu Ser Leu Gln Ala Phe Val Lys Asn Thr Gly Ile
65 70 75 80
Asn Leu Ser Ile Ile Asp Val Gly Trp Ala Pro Leu Ala Thr Ile Thr
85 90 95
Trp Gly Ser Pro Tyr Thr Leu Tyr Phe Leu Leu Ile Met Leu Ile Val
100 105 110
Asn Ile Val Met Ile Val Met Lys Lys Lys Arg Ile Pro
115 120 125
<210> 14
<211> 705
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (118)..(705)
<400> 14
ggatcgggcg caagcttaac gattcttttt aaaatcatta aattttaaaa caaatttcag 60
acatattgcc aaagttttga tattattact ataatatagt ttgtagagga gaataat 117
atg ggc caa gaa cct atc atc gaa tat caa aat atc aat aaa gtg tat 165
Met Gly Gln Glu Pro Ile Ile Glu Tyr Gln Asn Ile Asn Lys Val Tyr
1 5 10 15
ggg gaa aat gtt gcg gtt gaa gat att aac ctt aaa att tac cct ggt 213
Gly Glu Asn Val Ala Val Glu Asp Ile Asn Leu Lys Ile Tyr Pro Gly
20 25 30
gat ttc gtt tgt ttc atc ggt acg agt gga tca ggt aaa aca aca tta 261
Asp Phe Val Cys Phe Ile Gly Thr Ser Gly Ser Gly Lys Thr Thr Leu
35 40 45
atg cgt atg gtt aac cat atg tta aaa cca aca aat ggt act cta tta 309
Met Arg Met Val Asn His Met Leu Lys Pro Thr Asn Gly Thr Leu Leu
50 55 60
ttt aag gga aaa gat atc tct act att aac ccc att gaa tta aga cgc 357
Phe Lys Gly Lys Asp Ile Ser Thr Ile Asn Pro Ile Glu Leu Arg Arg
65 70 75 80
aga att gga tat gtt atc caa aac att ggt tta atg cct cat atg acc 405
Arg Ile Gly Tyr Val Ile Gln Asn Ile Gly Leu Met Pro His Met Thr
85 90 95
att tac gaa aat ata gtt ctt gta cca aaa tta ttg aaa tgg tca gaa 453
Ile Tyr Glu Asn Ile Val Leu Val Pro Lys Leu Leu Lys Trp Ser Glu
100 105 110
gaa gct aaa aga gct aaa gca agg gaa ctt att aaa tta gtt gaa tta 501
Glu Ala Lys Arg Ala Lys Ala Arg Glu Leu Ile Lys Leu Val Glu Leu
115 120 125
ccc gaa gaa tat ttg gat cgc tac cct agt gag ttg tct ggc ggt cag 549
Pro Glu Glu Tyr Leu Asp Arg Tyr Pro Ser Glu Leu Ser Gly Gly Gln
130 135 140
caa caa cgt atc ggt gtc att cgc gct ctt gca gca gac caa gat att 597
Gln Gln Arg Ile Gly Val Ile Arg Ala Leu Ala Ala Asp Gln Asp Ile
145 150 155 160
att tta atg gat gag cct ttt gga gct ctg gat cct att act aga gaa 645
Ile Leu Met Asp Glu Pro Phe Gly Ala Leu Asp Pro Ile Thr Arg Glu
165 170 175
ggt att caa gac ttt agt caa gtc tct tca gga aga aat ggg gga aaa 693
Gly Ile Gln Asp Phe Ser Gln Val Ser Ser Gly Arg Asn Gly Gly Lys
180 185 190
cta tca tct tag 705
Leu Ser Ser
195
<210> 15
<211> 195
<212> PRT
<213> group B streptococcus
<400> 15
Met Gly Gln Glu Pro Ile Ile Glu Tyr Gln Asn Ile Asn Lys Val Tyr
1 5 10 15
Gly Glu Asn Val Ala Val Glu Asp Ile Asn Leu Lys Ile Tyr Pro Gly
20 25 30
Asp Phe Val Cys Phe Ile Gly Thr Ser Gly Ser Gly Lys Thr Thr Leu
35 40 45
Met Arg Met Val Asn His Met Leu Lys Pro Thr Asn Gly Thr Leu Leu
50 55 60
Phe Lys Gly Lys Asp Ile Ser Thr Ile Asn Pro Ile Glu Leu Arg Arg
65 70 75 80
Arg Ile Gly Tyr Val Ile Gln Asn Ile Gly Leu Met Pro His Met Thr
85 90 95
Ile Tyr Glu Asn Ile Val Leu Val Pro Lys Leu Leu Lys Trp Ser Glu
100 105 110
Glu Ala Lys Arg Ala Lys Ala Arg Glu Leu Ile Lys Leu Val Glu Leu
115 120 125
Pro Glu Glu Tyr Leu Asp Arg Tyr Pro Ser Glu Leu Ser Gly Gly Gln
130 135 140
Gln Gln Arg Ile Gly Val Ile Arg Ala Leu Ala Ala Asp Gln Asp Ile
145 150 155 160
Ile Leu Met Asp Glu Pro Phe Gly Ala Leu Asp Pro Ile Thr Arg Glu
165 170 175
Gly Ile Gln Asp Phe Ser Gln Val Ser Ser Gly Arg Asn Gly Gly Lys
180 185 190
Leu Ser Ser
195
<210> 16
<211> 367
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(366)
<400> 16
atc cct tat agt gat gtt ttt gct aca gga gga ttt tta tac tat gta 48
Ile Pro Tyr Ser Asp Val Phe Ala Thr Gly Gly Phe Leu Tyr Tyr Val
1 5 10 15
acg att gct cta agt tac ctt tta ggg tct agt atc tgg tta ttt att 96
Thr Ile Ala Leu Ser Tyr Leu Leu Gly Ser Ser Ile Trp Leu Phe Ile
20 25 30
gta cag ttt att gct tac tat gta tct gga att tat ttt tat aaa tta 144
Val Gln Phe Ile Ala Tyr Tyr Val Ser Gly Ile Tyr Phe Tyr Lys Leu
35 40 45
gtt tat tat gtg gca caa agt gaa att gtc tcg ata ggc atg acg ttg 192
Val Tyr Tyr Val Ala Gln Ser Glu Ile Val Ser Ile Gly Met Thr Leu
50 55 60
att ttc tat ata atg aat att gtc tta gga ttc ggt ggt atg tac cca 240
Ile Phe Tyr Ile Met Asn Ile Val Leu Gly Phe Gly Gly Met Tyr Pro
65 70 75 80
ata cag tgg gca tta cct ttt atg ctc att tcg cta tgg ttt tta att 288
Ile Gln Trp Ala Leu Pro Phe Met Leu Ile Ser Leu Trp Phe Leu Ile
85 90 95
aaa ttt tgt gtc gat aat atc gtt gat gaa gca ttt ata ttt tat ggt 336
Lys Phe Cys Val Asp Asn Ile Val Asp Glu Ala Phe Ile Phe Tyr Gly
100 105 110
att tta gca gca ttc tca cta ttt ata gat c 367
Ile Leu Ala Ala Phe Ser Leu Phe Ile Asp
115 120
<210> 17
<211> 122
<212> PRT
<213> group B streptococcus
<400> 17
Ile Pro Tyr Ser Asp Val Phe Ala Thr Gly Gly Phe Leu Tyr Tyr Val
1 5 10 15
Thr Ile Ala Leu Ser Tyr Leu Leu Gly Ser Ser Ile Trp Leu Phe Ile
20 25 30
Val Gln Phe Ile Ala Tyr Tyr Val Ser Gly Ile Tyr Phe Tyr Lys Leu
35 40 45
Val Tyr Tyr Val Ala Gln Ser Glu Ile Val Ser Ile Gly Met Thr Leu
50 55 60
Ile Phe Tyr Ile Met Asn Ile Val Leu Gly Phe Gly Gly Met Tyr Pro
65 70 75 80
Ile Gln Trp Ala Leu Pro Phe Met Leu Ile Ser Leu Trp Phe Leu Ile
85 90 95
Lys Phe Cys Val Asp Asn Ile Val Asp Glu Ala Phe Ile Phe Tyr Gly
100 105 110
Ile Leu Ala Ala Phe Ser Leu Phe Ile Asp
115 120
<210> 18
<211> 570
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(570)
<400> 18
atg agg aaa cgt ttt tcc ttg cta aat ttt att gtt gtt act ttt att 48
Met Arg Lys Arg Phe Ser Leu Leu Asn Phe Ile Val Val Thr Phe Ile
1 5 10 15
ttc ttt ttc ttt att ctt ttt ccg ctt tta aac cat aag gga aaa gta 96
Phe Phe Phe Phe Ile Leu Phe Pro Leu Leu Asn His Lys Gly Lys Val
20 25 30
gat gct aat tct agg cag agt gtt acc tac acc aaa gaa gaa ttt ata 144
Asp Ala Asn Ser Arg Gln Ser Val Thr Tyr Thr Lys Glu Glu Phe Ile
35 40 45
caa aaa att gtg cca gat gcg caa gat cta gga aag tcg tac ggt att 192
Gln Lys Ile Val Pro Asp Ala Gln Asp Leu Gly Lys Ser Tyr Gly Ile
50 55 60
cgt cct tca ttt att att gca cag gcg gct ttg gat tct gat ttc gga 240
Arg Pro Ser Phe Ile Ile Ala Gln Ala Ala Leu Asp Ser Asp Phe Gly
65 70 75 80
gag aaa tat agc tat agt atc ata atc tgt tgg ttg ctt gca gaa cca 288
Glu Lys Tyr Ser Tyr Ser Ile Ile Ile Cys Trp Leu Leu Ala Glu Pro
85 90 95
gga acg ccc tca att acc tta aat gat agt agt aca gga aaa aaa cag 336
Gly Thr Pro Ser Ile Thr Leu Asn Asp Ser Ser Thr Gly Lys Lys Gln
100 105 110
gaa aag caa ttt act cat tat aaa tct tgg aag tat tca atg gat gat 384
Glu Lys Gln Phe Thr His Tyr Lys Ser Trp Lys Tyr Ser Met Asp Asp
115 120 125
tac ctt gct cat ata aaa tct gga gcg aca ggc aaa aaa gat tca tat 432
Tyr Leu Ala His Ile Lys Ser Gly Ala Thr Gly Lys Lys Asp Ser Tyr
130 135 140
act ata atg gtg tct gtt aaa aat cca aaa act tta gtg caa aaa tta 480
Thr Ile Met Val Ser Val Lys Asn Pro Lys Thr Leu Val Gln Lys Leu
145 150 155 160
caa gat agt ggt ttt gat aat gac aaa aag tac gct aaa aaa atg acg 528
Gln Asp Ser Gly Phe Asp Asn Asp Lys Lys Tyr Ala Lys Lys Met Thr
165 170 175
gaa atc att gat ttg tat gat tta aca aga tat gat aag tga 570
Glu Ile Ile Asp Leu Tyr Asp Leu Thr Arg Tyr Asp Lys
180 185 190
<210> 19
<211> 189
<212> PRT
<213> group B streptococcus
<400> 19
Met Arg Lys Arg Phe Ser Leu Leu Asn Phe Ile Val Val Thr Phe Ile
1 5 10 15
Phe Phe Phe Phe Ile Leu Phe Pro Leu Leu Asn His Lys Gly Lys Val
20 25 30
Asp Ala Asn Ser Arg Gln Ser Val Thr Tyr Thr Lys Glu Glu Phe Ile
35 40 45
Gln Lys Ile Val Pro Asp Ala Gln Asp Leu Gly Lys Ser Tyr Gly Ile
50 55 60
Arg Pro Ser Phe Ile Ile Ala Gln Ala Ala Leu Asp Ser Asp Phe Gly
65 70 75 80
Glu Lys Tyr Ser Tyr Ser Ile Ile Ile Cys Trp Leu Leu Ala Glu Pro
85 90 95
Gly Thr Pro Ser Ile Thr Leu Asn Asp Ser Ser Thr Gly Lys Lys Gln
100 105 110
Glu Lys Gln Phe Thr His Tyr Lys Ser Trp Lys Tyr Ser Met Asp Asp
115 120 125
Tyr Leu Ala His Ile Lys Ser Gly Ala Thr Gly Lys Lys Asp Ser Tyr
130 135 140
Thr Ile Met Val Ser Val Lys Asn Pro Lys Thr Leu Val Gln Lys Leu
145 150 155 160
Gln Asp Ser Gly Phe Asp Asn Asp Lys Lys Tyr Ala Lys Lys Met Thr
165 170 175
Glu Ile Ile Asp Leu Tyr Asp Leu Thr Arg Tyr Asp Lys
180 185
<210> 20
<211> 978
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(978)
<400> 20
atg ctt gtc atc att ttg atc att gta cta gct agt ctg aca gtg acg 48
Met Leu Val Ile Ile Leu Ile Ile Val Leu Ala Ser Leu Thr Val Thr
1 5 10 15
ata att tct tac cca aaa atg acg gaa tta aca aag tcc gtt gaa aaa 96
Ile Ile Ser Tyr Pro Lys Met Thr Glu Leu Thr Lys Ser Val Glu Lys
20 25 30
caa ctt gaa gat aat gct gat aat cta tca gac caa ctg aca tat cag 144
Gln Leu Glu Asp Asn Ala Asp Asn Leu Ser Asp Gln Leu Thr Tyr Gln
35 40 45
ata gaa gtg gcg caa aaa gat caa atc tac gtg act aat cag cta aac 192
Ile Glu Val Ala Gln Lys Asp Gln Ile Tyr Val Thr Asn Gln Leu Asn
50 55 60
cgt atg caa cag gaa att atc agt cgc tta ccg ata tgc gta cag aat 240
Arg Met Gln Gln Glu Ile Ile Ser Arg Leu Pro Ile Cys Val Gln Asn
65 70 75 80
aaa tca gca tta acg gag agt cga gat cga tca gac aaa cgc ttg gaa 288
Lys Ser Ala Leu Thr Glu Ser Arg Asp Arg Ser Asp Lys Arg Leu Glu
85 90 95
ttg att aac tcc aat tta tct cag tca gtt cag aaa atg caa gat tca 336
Leu Ile Asn Ser Asn Leu Ser Gln Ser Val Gln Lys Met Gln Asp Ser
100 105 110
atg aaa aac gct tgg atc aaa tgc gcc aaa ctg ttg agg aaa agc tgg 384
Met Lys Asn Ala Trp Ile Lys Cys Ala Lys Leu Leu Arg Lys Ser Trp
115 120 125
aaa aaa cgc tac aaa cgc gtt gca aac ttc ttt gaa act gta tcg cgt 432
Lys Lys Arg Tyr Lys Arg Val Ala Asn Phe Phe Glu Thr Val Ser Arg
130 135 140
caa cta gag agc gtc aat caa ggt ctg ggt aga tgg aaa ctg tgc caa 480
Gln Leu Glu Ser Val Asn Gln Gly Leu Gly Arg Trp Lys Leu Cys Gln
145 150 155 160
gat gtt ggt acc act gaa caa agt ctg tca aat act aag aca agg gga 528
Asp Val Gly Thr Thr Glu Gln Ser Leu Ser Asn Thr Lys Thr Arg Gly
165 170 175
ata tta ggg gag tta caa ctc ggt caa att ata gaa gat att atg aca 576
Ile Leu Gly Glu Leu Gln Leu Gly Gln Ile Ile Glu Asp Ile Met Thr
180 185 190
gtt agt caa tat gag aga gaa ttt cct acg gtg tct ggc tct tct gag 624
Val Ser Gln Tyr Glu Arg Glu Phe Pro Thr Val Ser Gly Ser Ser Glu
195 200 205
cgt gtt gaa tat gct att aaa tac ctg gaa atg gtc agg gag att ata 672
Arg Val Glu Tyr Ala Ile Lys Tyr Leu Glu Met Val Arg Glu Ile Ile
210 215 220
tct att tgc cta ttg act cta agt ttc tct aga aga tta tta ccg att 720
Ser Ile Cys Leu Leu Thr Leu Ser Phe Ser Arg Arg Leu Leu Pro Ile
225 230 235 240
ggg aga tgc tta tgg aat tgg gtg acc agg ttc aaa tgg aac tct att 768
Gly Arg Cys Leu Trp Asn Trp Val Thr Arg Phe Lys Trp Asn Ser Ile
245 250 255
cgt aat ctt tac tgg gca agt att cgt aaa ttt gca aaa gat ata aac 816
Arg Asn Leu Tyr Trp Ala Ser Ile Arg Lys Phe Ala Lys Asp Ile Asn
260 265 270
aat aag tac tta aat cct cct gaa acg aca aat ttt ggt atc atg ttc 864
Asn Lys Tyr Leu Asn Pro Pro Glu Thr Thr Asn Phe Gly Ile Met Phe
275 280 285
tta cca act gaa ggg ctc tat tct gaa gtg gta aga aat gca aca ttc 912
Leu Pro Thr Glu Gly Leu Tyr Ser Glu Val Val Arg Asn Ala Thr Phe
290 295 300
ttt gat agt cta aga cgt gac gaa aat att gta gta gct gga ccg tca 960
Phe Asp Ser Leu Arg Arg Asp Glu Asn Ile Val Val Ala Gly Pro Ser
305 310 315 320
acc tta tct gct tac taa 978
Thr Leu Ser Ala Tyr
325
<210> 21
<211> 325
<212> PRT
<213> group B streptococcus
<400> 21
Met Leu Val Ile Ile Leu Ile Ile Val Leu Ala Ser Leu Thr Val Thr
1 5 10 15
Ile Ile Ser Tyr Pro Lys Met Thr Glu Leu Thr Lys Ser Val Glu Lys
20 25 30
Gln Leu Glu Asp Asn Ala Asp Asn Leu Ser Asp Gln Leu Thr Tyr Gln
35 40 45
Ile Glu Val Ala Gln Lys Asp Gln Ile Tyr Val Thr Asn Gln Leu Asn
50 55 60
Arg Met Gln Gln Glu Ile Ile Ser Arg Leu Pro Ile Cys Val Gln Asn
65 70 75 80
Lys Ser Ala Leu Thr Glu Ser Arg Asp Arg Ser Asp Lys Arg Leu Glu
85 90 95
Leu Ile Asn Ser Asn Leu Ser Gln Ser Val Gln Lys Met Gln Asp Ser
100 105 110
Met Lys Asn Ala Trp Ile Lys Cys Ala Lys Leu Leu Arg Lys Ser Trp
115 120 125
Lys Lys Arg Tyr Lys Arg Val Ala Asn Phe Phe Glu Thr Val Ser Arg
130 135 140
Gln Leu Glu Ser Val Asn Gln Gly Leu Gly Arg Trp Lys Leu Cys Gln
145 150 155 160
Asp Val Gly Thr Thr Glu Gln Ser Leu Ser Asn Thr Lys Thr Arg Gly
165 170 175
Ile Leu Gly Glu Leu Gln Leu Gly Gln Ile Ile Glu Asp Ile Met Thr
180 185 190
Val Ser Gln Tyr Glu Arg Glu Phe Pro Thr Val Ser Gly Ser Ser Glu
195 200 205
Arg Val Glu Tyr Ala Ile Lys Tyr Leu Glu Met Val Arg Glu Ile Ile
210 215 220
Ser Ile Cys Leu Leu Thr Leu Ser Phe Ser Arg Arg Leu Leu Pro Ile
225 230 235 240
Gly Arg Cys Leu Trp Asn Trp Val Thr Arg Phe Lys Trp Asn Ser Ile
245 250 255
Arg Asn Leu Tyr Trp Ala Ser Ile Arg Lys Phe Ala Lys Asp Ile Asn
260 265 270
Asn Lys Tyr Leu Asn Pro Pro Glu Thr Thr Asn Phe Gly Ile Met Phe
275 280 285
Leu Pro Thr Glu Gly Leu Tyr Ser Glu Val Val Arg Asn Ala Thr Phe
290 295 300
Phe Asp Ser Leu Arg Arg Asp Glu Asn Ile Val Val Ala Gly Pro Ser
305 310 315 320
Thr Leu Ser Ala Tyr
325
<210> 22
<211> 579
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(579)
<400> 22
atg cga aaa gaa gtg aca cca gag atg ctt aac tat aat aag tat cct 48
Met Arg Lys Glu Val Thr Pro Glu Met Leu Asn Tyr Asn Lys Tyr Pro
1 5 10 15
ggc cca cag ttt att cac ttt gaa aat atc gtt aaa agt gat gat att 96
Gly Pro Gln Phe Ile His Phe Glu Asn Ile Val Lys Ser Asp Asp Ile
20 25 30
gaa ttt caa ctt gtt att aat gaa aaa tca gct ttt gat gtg act gtc 144
Glu Phe Gln Leu Val Ile Asn Glu Lys Ser Ala Phe Asp Val Thr Val
35 40 45
ttt gga caa cgt ttt tct gag att tta tta aaa tat gat ttt atc gtt 192
Phe Gly Gln Arg Phe Ser Glu Ile Leu Leu Lys Tyr Asp Phe Ile Val
50 55 60
ggc gat tgg ggt aac gag cag ttg agg cta aga ggc ttt tac aaa gat 240
Gly Asp Trp Gly Asn Glu Gln Leu Arg Leu Arg Gly Phe Tyr Lys Asp
65 70 75 80
gct agt acg att aga aaa aat agc cgg att tca cgt tta gaa gat tat 288
Ala Ser Thr Ile Arg Lys Asn Ser Arg Ile Ser Arg Leu Glu Asp Tyr
85 90 95
att aaa gag tat tgt aac ttt ggt tgt gct tat ttt gtg ttg gag aat 336
Ile Lys Glu Tyr Cys Asn Phe Gly Cys Ala Tyr Phe Val Leu Glu Asn
100 105 110
cca aat cct aga gat att aaa ttt gat gat gaa aga cct cat aag cgt 384
Pro Asn Pro Arg Asp Ile Lys Phe Asp Asp Glu Arg Pro His Lys Arg
115 120 125
cgt aag tca aga tcc aaa tca caa tca tca aag tca caa act aga aat 432
Arg Lys Ser Arg Ser Lys Ser Gln Ser Ser Lys Ser Gln Thr Arg Asn
130 135 140
aat cgt tcc cag tca aat gcc aat gct cat ttt aca agt aaa aag cgt 480
Asn Arg Ser Gln Ser Asn Ala Asn Ala His Phe Thr Ser Lys Lys Arg
145 150 155 160
aaa gac aca aaa cgc cgt caa gaa cgt cat att aaa gaa gag caa gat 528
Lys Asp Thr Lys Arg Arg Gln Glu Arg His Ile Lys Glu Glu Gln Asp
165 170 175
aag gaa atg acc tct gca aag cag cat ttg tta ttc gta aga aaa aat 576
Lys Glu Met Thr Ser Ala Lys Gln His Leu Leu Phe Val Arg Lys Asn
180 185 190
taa 579
<210> 23
<211> 192
<212> PRT
<213> group B streptococcus
<400> 23
Met Arg Lys Glu Val Thr Pro Glu Met Leu Asn Tyr Asn Lys Tyr Pro
1 5 10 15
Gly Pro Gln Phe Ile His Phe Glu Asn Ile Val Lys Ser Asp Asp Ile
20 25 30
Glu Phe Gln Leu Val Ile Asn Glu Lys Ser Ala Phe Asp Val Thr Val
35 40 45
Phe Gly Gln Arg Phe Ser Glu Ile Leu Leu Lys Tyr Asp Phe Ile Val
50 55 60
Gly Asp Trp Gly Asn Glu Gln Leu Arg Leu Arg Gly Phe Tyr Lys Asp
65 70 75 80
Ala Ser Thr Ile Arg Lys Asn Ser Arg Ile Ser Arg Leu Glu Asp Tyr
85 90 95
Ile Lys Glu Tyr Cys Asn Phe Gly Cys Ala Tyr Phe Val Leu Glu Asn
100 105 110
Pro Asn Pro Arg Asp Ile Lys Phe Asp Asp Glu Arg Pro His Lys Arg
115 120 125
Arg Lys Ser Arg Ser Lys Ser Gln Ser Ser Lys Ser Gln Thr Arg Asn
130 135 140
Asn Arg Ser Gln Ser Asn Ala Asn Ala His Phe Thr Ser Lys Lys Arg
145 150 155 160
Lys Asp Thr Lys Arg Arg Gln Glu Arg His Ile Lys Glu Glu Gln Asp
165 170 175
Lys Glu Met Thr Ser Ala Lys Gln His Leu Leu Phe Val Arg Lys Asn
180 185 190
<210> 24
<211> 609
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(609)
<400> 24
atg aca ata aaa aaa gtg tta agt gta aca gga att att tta gtg aca 48
Met Thr Ile Lys Lys Val Leu Ser Val Thr Gly Ile Ile Leu Val Thr
1 5 10 15
gta gcg tct cta gct gct tgt agc tca aaa tct cat act act aag acg 96
Val Ala Ser Leu Ala Ala Cys Ser Ser Lys Ser His Thr Thr Lys Thr
20 25 30
ggc aaa aaa gaa gtt aat ttt gca act gtt gga aca acg gca cct ttt 144
Gly Lys Lys Glu Val Asn Phe Ala Thr Val Gly Thr Thr Ala Pro Phe
35 40 45
tct tat gtg aag gat ggg aaa ctg act ggc ttt gat att gaa gta gcc 192
Ser Tyr Val Lys Asp Gly Lys Leu Thr Gly Phe Asp Ile Glu Val Ala
50 55 60
aaa gct gtt ttt aaa ggt tca gat aac tat aaa gtc act ttt aaa aaa 240
Lys Ala Val Phe Lys Gly Ser Asp Asn Tyr Lys Val Thr Phe Lys Lys
65 70 75 80
aca gaa tgg tca tcg gta ttt acc ggc att gat tca gga aag ttt caa 288
Thr Glu Trp Ser Ser Val Phe Thr Gly Ile Asp Ser Gly Lys Phe Gln
85 90 95
atg ggt gga aat aat att tct tat tca tca gag aga tct caa aaa tay 336
Met Gly Gly Asn Asn Ile Ser Tyr Ser Ser Glu Arg Ser Gln Lys Tyr
100 105 110
tta ttt tca tac cca ata ggc tct act cct tca gtt tta gca gtt cct 384
Leu Phe Ser Tyr Pro Ile Gly Ser Thr Pro Ser Val Leu Ala Val Pro
115 120 125
aag aat agt aat atc aaa gct tat aat gat att agt ggt cat aaa aca 432
Lys Asn Ser Asn Ile Lys Ala Tyr Asn Asp Ile Ser Gly His Lys Thr
130 135 140
cag gtt gtc caa gga acg aca act gcc aag caa tta gaa aat ttc aat 480
Gln Val Val Gln Gly Thr Thr Thr Ala Lys Gln Leu Glu Asn Phe Asn
145 150 155 160
aaa gag cat cag aaa aat cct gtt act cta aaa tat act aat gaa aat 528
Lys Glu His Gln Lys Asn Pro Val Thr Leu Lys Tyr Thr Asn Glu Asn
165 170 175
att aca cag att cta acg aat ttg agt gat gga aaa gct gat ttt aaa 576
Ile Thr Gln Ile Leu Thr Asn Leu Ser Asp Gly Lys Ala Asp Phe Lys
180 185 190
ctt ttg acg gac caa ctg tta acg cta tta taa 609
Leu Leu Thr Asp Gln Leu Leu Thr Leu Leu
195 200
<210> 25
<211> 202
<212> PRT
<213> group B streptococcus
<400> 25
Met Thr Ile Lys Lys Val Leu Ser Val Thr Gly Ile Ile Leu Val Thr
1 5 10 15
Val Ala Ser Leu Ala Ala Cys Ser Ser Lys Ser His Thr Thr Lys Thr
20 25 30
Gly Lys Lys Glu Val Asn Phe Ala Thr Val Gly Thr Thr Ala Pro Phe
35 40 45
Ser Tyr Val Lys Asp Gly Lys Leu Thr Gly Phe Asp Ile Glu Val Ala
50 55 60
Lys Ala Val Phe Lys Gly Ser Asp Asn Tyr Lys Val Thr Phe Lys Lys
65 70 75 80
Thr Glu Trp Ser Ser Val Phe Thr Gly Ile Asp Ser Gly Lys Phe Gln
85 90 95
Met Gly Gly Asn Asn Ile Ser Tyr Ser Ser Glu Arg Ser Gln Lys Tyr
100 105 110
Leu Phe Ser Tyr Pro Ile Gly Ser Thr Pro Ser Val Leu Ala Val Pro
115 120 125
Lys Asn Ser Asn Ile Lys Ala Tyr Asn Asp Ile Ser Gly His Lys Thr
130 135 140
Gln Val Val Gln Gly Thr Thr Thr Ala Lys Gln Leu Glu Asn Phe Asn
145 150 155 160
Lys Glu His Gln Lys Asn Pro Val Thr Leu Lys Tyr Thr Asn Glu Asn
165 170 175
Ile Thr Gln Ile Leu Thr Asn Leu Ser Asp Gly Lys Ala Asp Phe Lys
180 185 190
Leu Leu Thr Asp Gln Leu Leu Thr Leu Leu
195 200
<210> 26
<211> 357
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(357)
<400> 26
atg aag aat ata aca aag cta tca act gtt gct tta agc cta cta ctt 48
Met Lys Asn Ile Thr Lys Leu Ser Thr Val Ala Leu Ser Leu Leu Leu
1 5 10 15
tgt acg gcg tgt gct gca tca aac acg tct aca tct aaa aca cag tct 96
Cys Thr Ala Cys Ala Ala Ser Asn Thr Ser Thr Ser Lys Thr Gln Ser
20 25 30
cat cat cct aaa caa act aaa ctc aca gat aag caa aaa gaa gaa ccc 144
His His Pro Lys Gln Thr Lys Leu Thr Asp Lys Gln Lys Glu Glu Pro
35 40 45
aaa aac aaa gaa gct gct gat caa gag atg cat ccc caa ggc gct gtt 192
Lys Asn Lys Glu Ala Ala Asp Gln Glu Met His Pro Gln Gly Ala Val
50 55 60
gat ttg aca aaa tat aag gca aaa ccg gtc aaa gat tat gga aaa aaa 240
Asp Leu Thr Lys Tyr Lys Ala Lys Pro Val Lys Asp Tyr Gly Lys Lys
65 70 75 80
atc gat gtt ggt gat ggc aag aaa atg aac att tat gaa act ggt cag 288
Ile Asp Val Gly Asp Gly Lys Lys Met Asn Ile Tyr Glu Thr Gly Gln
85 90 95
gga aaa att cca att gtt ttt att cct ggt caa gct gag att cgc cac 336
Gly Lys Ile Pro Ile Val Phe Ile Pro Gly Gln Ala Glu Ile Arg His
100 105 110
gct atg ctt ata aga att taa 357
Ala Met Leu Ile Arg Ile
115
<210> 27
<211> 118
<212> PRT
<213> group B streptococcus
<400> 27
Met Lys Asn Ile Thr Lys Leu Ser Thr Val Ala Leu Ser Leu Leu Leu
1 5 10 15
Cys Thr Ala Cys Ala Ala Ser Asn Thr Ser Thr Ser Lys Thr Gln Ser
20 25 30
His His Pro Lys Gln Thr Lys Leu Thr Asp Lys Gln Lys Glu Glu Pro
35 40 45
Lys Asn Lys Glu Ala Ala Asp Gln Glu Met His Pro Gln Gly Ala Val
50 55 60
Asp Leu Thr Lys Tyr Lys Ala Lys Pro Val Lys Asp Tyr Gly Lys Lys
65 70 75 80
Ile Asp Val Gly Asp Gly Lys Lys Met Asn Ile Tyr Glu Thr Gly Gln
85 90 95
Gly Lys Ile Pro Ile Val Phe Ile Pro Gly Gln Ala Glu Ile Arg His
100 105 110
Ala Met Leu Ile Arg Ile
115
<210> 28
<211> 1191
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(1191)
<400> 28
gtg aat gaa tcg acc atc aga aaa gaa ttt aaa ata gtt gtt ttt aaa 48
Val Asn Glu Ser Thr Ile Arg Lys Glu Phe Lys Ile Val Val Phe Lys
1 5 10 15
tgg atc tta aat aat caa gca gtt att gct ctc atg att acc ttt ttg 96
Trp Ile Leu Asn Asn Gln Ala Val Ile Ala Leu Met Ile Thr Phe Leu
20 25 30
gta ttt tta acg att ttt att ttt acc aaa atc tct ttt atg ttt aaa 144
Val Phe Leu Thr Ile Phe Ile Phe Thr Lys Ile Ser Phe Met Phe Lys
35 40 45
cct gtg ttt gat ttt ctt gct gtg ctg ata ttg ccg ctt gta att tct 192
Pro Val Phe Asp Phe Leu Ala Val Leu Ile Leu Pro Leu Val Ile Ser
50 55 60
ggc ttg ctt tat tac cta tta aaa cct atg gtt aca ttt tta gag aag 240
Gly Leu Leu Tyr Tyr Leu Leu Lys Pro Met Val Thr Phe Leu Glu Lys
65 70 75 80
cgg gga att aag cgt gta aca gcg ata tta tca gtt ttt act att ata 288
Arg Gly Ile Lys Arg Val Thr Ala Ile Leu Ser Val Phe Thr Ile Ile
85 90 95
atc ctt ctg tta att tgg gca atg tct agt ttt att ccc atg atg agt 336
Ile Leu Leu Leu Ile Trp Ala Met Ser Ser Phe Ile Pro Met Met Ser
100 105 110
aat caa tta cgc cat ttt atg gaa gat ctc cct tca tat gtg aat aaa 384
Asn Gln Leu Arg His Phe Met Glu Asp Leu Pro Ser Tyr Val Asn Lys
115 120 125
gtg caa atg gaa aca agt tcg ttt ata gat cac aac cct tgg tta aaa 432
Val Gln Met Glu Thr Ser Ser Phe Ile Asp His Asn Pro Trp Leu Lys
130 135 140
tct tat aaa ggg gaa ata tcg agc atg tta tct aat atc agt agc caa 480
Ser Tyr Lys Gly Glu Ile Ser Ser Met Leu Ser Asn Ile Ser Ser Gln
145 150 155 160
gcg gtc tct tat gct gaa aaa ttt tca aag aat gtt tta gat tgg gca 528
Ala Val Ser Tyr Ala Glu Lys Phe Ser Lys Asn Val Leu Asp Trp Ala
165 170 175
gga aat tta gct agt aca gtt gca cgt gtg aca gta gca aca atc atg 576
Gly Asn Leu Ala Ser Thr Val Ala Arg Val Thr Val Ala Thr Ile Met
180 185 190
gct ccc ttt att ttg ttt tat ctt tta aga gat agt cgc aac atg aag 624
Ala Pro Phe Ile Leu Phe Tyr Leu Leu Arg Asp Ser Arg Asn Met Lys
195 200 205
aat ggt ttc tta atg gtt tta cca acc aaa cta cgc caa cca gct gat 672
Asn Gly Phe Leu Met Val Leu Pro Thr Lys Leu Arg Gln Pro Ala Asp
210 215 220
cgt att ttg cga gaa atg aat agt caa atg tca gga tat gtg caa gga 720
Arg Ile Leu Arg Glu Met Asn Ser Gln Met Ser Gly Tyr Val Gln Gly
225 230 235 240
caa atc att gtt gct att act gtt ggt gtt att ttt tca ata atg tat 768
Gln Ile Ile Val Ala Ile Thr Val Gly Val Ile Phe Ser Ile Met Tyr
245 250 255
agt att ata ggc ctt aga tat ggc gtg aca tta ggg att att gcc ggt 816
Ser Ile Ile Gly Leu Arg Tyr Gly Val Thr Leu Gly Ile Ile Ala Gly
260 265 270
gtg tta aat atg gtt ccc tat ttg gga agt ttt gtc gcc caa att cca 864
Val Leu Asn Met Val Pro Tyr Leu Gly Ser Phe Val Ala Gln Ile Pro
275 280 285
gtg ttt atc tta gcg ctt gtc gca gga cct gtt atg gtt gtt aaa gtt 912
Val Phe Ile Leu Ala Leu Val Ala Gly Pro Val Met Val Val Lys Val
290 295 300
gcg att gtt ttt gtt att gag caa act cta gag gga cgc ttt gtc tca 960
Ala Ile Val Phe Val Ile Glu Gln Thr Leu Glu Gly Arg Phe Val Ser
305 310 315 320
cct ttg gtt tta ggt aat aaa ctt agc att cat cca att aca att atg 1008
Pro Leu Val Leu Gly Asn Lys Leu Ser Ile His Pro Ile Thr Ile Met
325 330 335
ttt att tta tta acc tct gga gcg atg ttt ggt gtt tgg gga gta ttc 1056
Phe Ile Leu Leu Thr Ser Gly Ala Met Phe Gly Val Trp Gly Val Phe
340 345 350
ctc agt att ccg att tat gca tct atc aaa gtt gtt gtt aaa gaa ttg 1104
Leu Ser Ile Pro Ile Tyr Ala Ser Ile Lys Val Val Val Lys Glu Leu
355 360 365
ttt gat tgg tac aaa gct gtc agt ggg cta tat aca ata gat gtt gtt 1152
Phe Asp Trp Tyr Lys Ala Val Ser Gly Leu Tyr Thr Ile Asp Val Val
370 375 380
act gaa gaa aga agt gaa gaa gtt aaa aat gtt gaa tag 1191
Thr Glu Glu Arg Ser Glu Glu Val Lys Asn Val Glu
385 390 395
<210> 29
<211> 396
<212> PRT
<213> group B streptococcus
<400> 29
Val Asn Glu Ser Thr Ile Arg Lys Glu Phe Lys Ile Val Val Phe Lys
1 5 10 15
Trp Ile Leu Asn Asn Gln Ala Val Ile Ala Leu Met Ile Thr Phe Leu
20 25 30
Val Phe Leu Thr Ile Phe Ile Phe Thr Lys Ile Ser Phe Met Phe Lys
35 40 45
Pro Val Phe Asp Phe Leu Ala Val Leu Ile Leu Pro Leu Val Ile Ser
50 55 60
Gly Leu Leu Tyr Tyr Leu Leu Lys Pro Met Val Thr Phe Leu Glu Lys
65 70 75 80
Arg Gly Ile Lys Arg Val Thr Ala Ile Leu Ser Val Phe Thr Ile Ile
85 90 95
Ile Leu Leu Leu Ile Trp Ala Met Ser Ser Phe Ile Pro Met Met Ser
100 105 110
Asn Gln Leu Arg His Phe Met Glu Asp Leu Pro Ser Tyr Val Asn Lys
115 120 125
Val Gln Met Glu Thr Ser Ser Phe Ile Asp His Asn Pro Trp Leu Lys
130 135 140
Ser Tyr Lys Gly Glu Ile Ser Ser Met Leu Ser Asn Ile Ser Ser Gln
145 150 155 160
Ala Val Ser Tyr Ala Glu Lys Phe Ser Lys Asn Val Leu Asp Trp Ala
165 170 175
Gly Asn Leu Ala Ser Thr Val Ala Arg Val Thr Val Ala Thr Ile Met
180 185 190
Ala Pro Phe Ile Leu Phe Tyr Leu Leu Arg Asp Ser Arg Asn Met Lys
195 200 205
Asn Gly Phe Leu Met Val Leu Pro Thr Lys Leu Arg Gln Pro Ala Asp
210 215 220
Arg Ile Leu Arg Glu Met Asn Ser Gln Met Ser Gly Tyr Val Gln Gly
225 230 235 240
Gln Ile Ile Val Ala Ile Thr Val Gly Val Ile Phe Ser Ile Met Tyr
245 250 255
Ser Ile Ile Gly Leu Arg Tyr Gly Val Thr Leu Gly Ile Ile Ala Gly
260 265 270
Val Leu Asn Met Val Pro Tyr Leu Gly Ser Phe Val Ala Gln Ile Pro
275 280 285
Val Phe Ile Leu Ala Leu Val Ala Gly Pro Val Met Val Val Lys Val
290 295 300
Ala Ile Val Phe Val Ile Glu Gln Thr Leu Glu Gly Arg Phe Val Ser
305 310 315 320
Pro Leu Val Leu Gly Asn Lys Leu Ser Ile His Pro Ile Thr Ile Met
325 330 335
Phe Ile Leu Leu Thr Ser Gly Ala Met Phe Gly Val Trp Gly Val Phe
340 345 350
Leu Ser Ile Pro Ile Tyr Ala Ser Ile Lys Val Val Val Lys Glu Leu
355 360 365
Phe Asp Trp Tyr Lys Ala Val Ser Gly Leu Tyr Thr Ile Asp Val Val
370 375 380
Thr Glu Glu Arg Ser Glu Glu Val Lys Asn Val Glu
385 390 395
<210> 30
<211> 1230
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(1230)
<400> 30
atg ttt atg gga atc cca caa tat ttc ttc tac ctt atc tta gct gtc 48
Met Phe Met Gly Ile Pro Gln Tyr Phe Phe Tyr Leu Ile Leu Ala Val
1 5 10 15
cta cca att tac atc ggc tta ttc ttt aag aag cgt ttt gcc tta tat 96
Leu Pro Ile Tyr Ile Gly Leu Phe Phe Lys Lys Arg Phe Ala Leu Tyr
20 25 30
gag att att ttt agt cta agt ttt att gta atg atg ttg act ggt agt 144
Glu Ile Ile Phe Ser Leu Ser Phe Ile Val Met Met Leu Thr Gly Ser
35 40 45
act ttt aat caa ttg aag tca cta ttg gca tac gtt gtc gga cag tct 192
Thr Phe Asn Gln Leu Lys Ser Leu Leu Ala Tyr Val Val Gly Gln Ser
50 55 60
ctg cta gtt ttt atc tat aaa gct tac cgg aaa cga ttt aat cat act 240
Leu Leu Val Phe Ile Tyr Lys Ala Tyr Arg Lys Arg Phe Asn His Thr
65 70 75 80
ttg gtc ttt tat gta acg gtt tgt tta tct att ttt ccg cta ttt ttg 288
Leu Val Phe Tyr Val Thr Val Cys Leu Ser Ile Phe Pro Leu Phe Leu
85 90 95
gta aaa tta att cca gct ata tct gag gat ggg cat cag tca ctt ttt 336
Val Lys Leu Ile Pro Ala Ile Ser Glu Asp Gly His Gln Ser Leu Phe
100 105 110
ggg ttt cta gga att tct tac ctt act ttt aga gct gtt gct atg att 384
Gly Phe Leu Gly Ile Ser Tyr Leu Thr Phe Arg Ala Val Ala Met Ile
115 120 125
att gaa atg aga gac ggt gtc ttg aaa gaa ttt act tta tgg gaa ttc 432
Ile Glu Met Arg Asp Gly Val Leu Lys Glu Phe Thr Leu Trp Glu Phe
130 135 140
tta aga ttt tta ctc ttc ttt cca act ttc tca agt gga cca att gat 480
Leu Arg Phe Leu Leu Phe Phe Pro Thr Phe Ser Ser Gly Pro Ile Asp
145 150 155 160
cgt ttt aaa cga ttc aat gag gat tac att aat atc cca gat cga aac 528
Arg Phe Lys Arg Phe Asn Glu Asp Tyr Ile Asn Ile Pro Asp Arg Asn
165 170 175
gaa ctc cta gat atg tta ggt caa gcg att cat tat ttg atg tta ggt 576
Glu Leu Leu Asp Met Leu Gly Gln Ala Ile His Tyr Leu Met Leu Gly
180 185 190
ttt ctc tat aag ttt att tta gcc tat att ttt gga agt ctg att atg 624
Phe Leu Tyr Lys Phe Ile Leu Ala Tyr Ile Phe Gly Ser Leu Ile Met
195 200 205
cct cct cta aaa gaa tta gcg cta gaa cag ggt ggt gtg ttt aat tgg 672
Pro Pro Leu Lys Glu Leu Ala Leu Glu Gln Gly Gly Val Phe Asn Trp
210 215 220
cca aca ctt ggg gtt atg tat gcc ttt ggt ttt gat ttg ttc ttt gat 720
Pro Thr Leu Gly Val Met Tyr Ala Phe Gly Phe Asp Leu Phe Phe Asp
225 230 235 240
ttt gca ggt tac aca atg ttt gcg ttg gct att tct aac cta atg ggg 768
Phe Ala Gly Tyr Thr Met Phe Ala Leu Ala Ile Ser Asn Leu Met Gly
245 250 255
att aag tct ccg att aac ttt gac aaa cct ttc aaa tca cgc gac cta 816
Ile Lys Ser Pro Ile Asn Phe Asp Lys Pro Phe Lys Ser Arg Asp Leu
260 265 270
aaa gaa ttt tgg aat aga tgg cat atg agc ctt tct ttc tgg ttt aga 864
Lys Glu Phe Trp Asn Arg Trp His Met Ser Leu Ser Phe Trp Phe Arg
275 280 285
gac ttt gtt ttc atg agg ctt gtt aag ctt tta gtt aaa aat aaa gtt 912
Asp Phe Val Phe Met Arg Leu Val Lys Leu Leu Val Lys Asn Lys Val
290 295 300
ttt aaa aac cgt aat gtt act tca agt gta gct tat att atc aat atg 960
Phe Lys Asn Arg Asn Val Thr Ser Ser Val Ala Tyr Ile Ile Asn Met
305 310 315 320
ctt ctt atg gga ttc tgg cat ggg tta act tgg tac tat ata gcc tat 1008
Leu Leu Met Gly Phe Trp His Gly Leu Thr Trp Tyr Tyr Ile Ala Tyr
325 330 335
ggt ctc ttt cat ggg att ggc cta gtt att aat gac gct tgg gta cgt 1056
Gly Leu Phe His Gly Ile Gly Leu Val Ile Asn Asp Ala Trp Val Arg
340 345 350
aag aag aaa aat ayt aat aaa gaa aga aga ttg gct aaa aaa cca ctt 1104
Lys Lys Lys Asn Xaa Asn Lys Glu Arg Arg Leu Ala Lys Lys Pro Leu
355 360 365
tta cca gaa aac aaa tgg act tat gct ttg ggt gtc ttc atc acc ttt 1152
Leu Pro Glu Asn Lys Trp Thr Tyr Ala Leu Gly Val Phe Ile Thr Phe
370 375 380
aat gta gtt atg ttt tct ttc ttg att ttt tca gga ttt tta gat ctt 1200
Asn Val Val Met Phe Ser Phe Leu Ile Phe Ser Gly Phe Leu Asp Leu
385 390 395 400
ttg tgg ttc cca caa ccg cat aac aaa taa 1230
Leu Trp Phe Pro Gln Pro His Asn Lys
405 410
<210> 31
<211> 409
<212> PRT
<213> group B streptococcus
<400> 31
Met Phe Met Gly Ile Pro Gln Tyr Phe Phe Tyr Leu Ile Leu Ala Val
1 5 10 15
Leu Pro Ile Tyr Ile Gly Leu Phe Phe Lys Lys Arg Phe Ala Leu Tyr
20 25 30
Glu Ile Ile Phe Ser Leu Ser Phe Ile Val Met Met Leu Thr Gly Ser
35 40 45
Thr Phe Asn Gln Leu Lys Ser Leu Leu Ala Tyr Val Val Gly Gln Ser
50 55 60
Leu Leu Val Phe Ile Tyr Lys Ala Tyr Arg Lys Arg Phe Asn His Thr
65 70 75 80
Leu Val Phe Tyr Val Thr Val Cys Leu Ser Ile Phe Pro Leu Phe Leu
85 90 95
Val Lys Leu Ile Pro Ala Ile Ser Glu Asp Gly His Gln Ser Leu Phe
100 105 110
Gly Phe Leu Gly Ile Ser Tyr Leu Thr Phe Arg Ala Val Ala Met Ile
115 120 125
Ile Glu Met Arg Asp Gly Val Leu Lys Glu Phe Thr Leu Trp Glu Phe
130 135 140
Leu Arg Phe Leu Leu Phe Phe Pro Thr Phe Ser Ser Gly Pro Ile Asp
145 150 155 160
Arg Phe Lys Arg Phe Asn Glu Asp Tyr Ile Asn Ile Pro Asp Arg Asn
165 170 175
Glu Leu Leu Asp Met Leu Gly Gln Ala Ile His Tyr Leu Met Leu Gly
180 185 190
Phe Leu Tyr Lys Phe Ile Leu Ala Tyr Ile Phe Gly Ser Leu Ile Met
195 200 205
Pro Pro Leu Lys Glu Leu Ala Leu Glu Gln Gly Gly Val Phe Asn Trp
210 215 220
Pro Thr Leu Gly Val Met Tyr Ala Phe Gly Phe Asp Leu Phe Phe Asp
225 230 235 240
Phe Ala Gly Tyr Thr Met Phe Ala Leu Ala Ile Ser Asn Leu Met Gly
245 250 255
Ile Lys Ser Pro Ile Asn Phe Asp Lys Pro Phe Lys Ser Arg Asp Leu
260 265 270
Lys Glu Phe Trp Asn Arg Trp His Met Ser Leu Ser Phe Trp Phe Arg
275 280 285
Asp Phe Val Phe Met Arg Leu Val Lys Leu Leu Val Lys Asn Lys Val
290 295 300
Phe Lys Asn Arg Asn Val Thr Ser Ser Val Ala Tyr Ile Ile Asn Met
305 310 315 320
Leu Leu Met Gly Phe Trp His Gly Leu Thr Trp Tyr Tyr Ile Ala Tyr
325 330 335
Gly Leu Phe His Gly Ile Gly Leu Val Ile Asn Asp Ala Trp Val Arg
340 345 350
Lys Lys Lys Asn Xaa Asn Lys Glu Arg Arg Leu Ala Lys Lys Pro Leu
355 360 365
Leu Pro Glu Asn Lys Trp Thr Tyr Ala Leu Gly Val Phe Ile Thr Phe
370 375 380
Asn Val Val Met Phe Ser Phe Leu Ile Phe Ser Gly Phe Leu Asp Leu
385 390 395 400
Leu Trp Phe Pro Gln Pro His Asn Lys
405
<210> 32
<211> 100
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(99)
<400> 32
atg aat aaa ata acg aca tta tca acc atc gcc ctg act tta atg ctt 48
Met Asn Lys Ile Thr Thr Leu Ser Thr Ile Ala Leu Thr Leu Met Leu
1 5 10 15
tgc gtt gga tgt tct gcc aat aaa gat aat caa aaa act aaa act gag 96
Cys Val Gly Cys Ser Ala Asn Lys Asp Asn Gln Lys Thr Lys Thr Glu
20 25 30
gat c 100
Asp
<210> 33
<211> 33
<212> PRT
<213> group B streptococcus
<400> 33
Met Asn Lys Ile Thr Thr Leu Ser Thr Ile Ala Leu Thr Leu Met Leu
1 5 10 15
Cys Val Gly Cys Ser Ala Asn Lys Asp Asn Gln Lys Thr Lys Thr Glu
20 25 30
Asp
<210> 34
<211> 654
<212> DNA
<213> group B streptococcus
<220>
<221> CDS
<222> (1)..(654)
<400> 34
gat cga ggc tat caa gaa gca atg gct aaa cta agg aaa act tac ggc 48
Asp Arg Gly Tyr Gln Glu Ala Met Ala Lys Leu Arg Lys Thr Tyr Gly
1 5 10 15
gaa tat ggt tta ggg gtt tct aca gga tta gat tta cct gaa tca gaa 96
Glu Tyr Gly Leu Gly Val Ser Thr Gly Leu Asp Leu Pro Glu Ser Glu
20 25 30
ggt tat gta cct gga aaa tac agc tta gga aca act cta atg gaa tcg 144
Gly Tyr Val Pro Gly Lys Tyr Ser Leu Gly Thr Thr Leu Met Glu Ser
35 40 45
ttc ggt cag tat gat gcc tat aca cca atg caa ctt ggt cag tat atc 192
Phe Gly Gln Tyr Asp Ala Tyr Thr Pro Met Gln Leu Gly Gln Tyr Ile
50 55 60
tca act att gcg aat aat ggg aat cgt tta gca cct cac gtg gtt tca 240
Ser Thr Ile Ala Asn Asn Gly Asn Arg Leu Ala Pro His Val Val Ser
65 70 75 80
gat atc tat gaa ggg aat gat tct aat aag ttc gct caa ttg gtt cgt 288
Asp Ile Tyr Glu Gly Asn Asp Ser Asn Lys Phe Ala Gln Leu Val Arg
85 90 95
tca atc act cct aaa aca cta aat aag ata gct atc tca gat caa gag 336
Ser Ile Thr Pro Lys Thr Leu Asn Lys Ile Ala Ile Ser Asp Gln Glu
100 105 110
tta gcc att att caa gaa ggt ttt tat aac gtt gtc aat agt gga agt 384
Leu Ala Ile Ile Gln Glu Gly Phe Tyr Asn Val Val Asn Ser Gly Ser
115 120 125
ggc tat gca act ggt acg tca atg agg ggg aat gtg aca acc att agy 432
Gly Tyr Ala Thr Gly Thr Ser Met Arg Gly Asn Val Thr Thr Ile Xaa
130 135 140
ggt aaa act ggt acc gct gaa aca ttt gct aaa aat ata aat gga caa 480
Gly Lys Thr Gly Thr Ala Glu Thr Phe Ala Lys Asn Ile Asn Gly Gln
145 150 155 160
aca gtt tct acc tac aac tta aac gct att gcc tac gat act aat cgt 528
Thr Val Ser Thr Tyr Asn Leu Asn Ala Ile Ala Tyr Asp Thr Asn Arg
165 170 175
aaa ata gca gta gcg gta atg tat ccg cat gtt aca act gat aca aca 576
Lys Ile Ala Val Ala Val Met Tyr Pro His Val Thr Thr Asp Thr Thr
180 185 190
aaa tcc cat caa tta gtt gca cga gat atg att gat caa tat att tca 624
Lys Ser His Gln Leu Val Ala Arg Asp Met Ile Asp Gln Tyr Ile Ser
195 200 205
cag tca cag gac aat aag aga gga cat tga 654
Gln Ser Gln Asp Asn Lys Arg Gly His
210 215
<210> 35
<211> 217
<212> PRT
<213> group B streptococcus
<400> 35
Asp Arg Gly Tyr Gln Glu Ala Met Ala Lys Leu Arg Lys Thr Tyr Gly
1 5 10 15
Glu Tyr Gly Leu Gly Val Ser Thr Gly Leu Asp Leu Pro Glu Ser Glu
20 25 30
Gly Tyr Val Pro Gly Lys Tyr Ser Leu Gly Thr Thr Leu Met Glu Ser
35 40 45
Phe Gly Gln Tyr Asp Ala Tyr Thr Pro Met Gln Leu Gly Gln Tyr Ile
50 55 60
Ser Thr Ile Ala Asn Asn Gly Asn Arg Leu Ala Pro His Val Val Ser
65 70 75 80
Asp Ile Tyr Glu Gly Asn Asp Ser Asn Lys Phe Ala Gln Leu Val Arg
85 90 95
Ser Ile Thr Pro Lys Thr Leu Asn Lys Ile Ala Ile Ser Asp Gln Glu
100 105 110
Leu Ala Ile Ile Gln Glu Gly Phe Tyr Asn Val Val Asn Ser Gly Ser
115 120 125
Gly Tyr Ala Thr Gly Thr Ser Met Arg Gly Asn Val Thr Thr Ile Xaa
130 135 140
Gly Lys Thr Gly Thr Ala Glu Thr Phe Ala Lys Asn Ile Asn Gly Gln
145 150 155 160
Thr Val Ser Thr Tyr Asn Leu Asn Ala Ile Ala Tyr Asp Thr Asn Arg
165 170 175
Lys Ile Ala Val Ala Val Met Tyr Pro His Val Thr Thr Asp Thr Thr
180 185 190
Lys Ser His Gln Leu Val Ala Arg Asp Met Ile Asp Gln Tyr Ile Ser
195 200 205
Gln Ser Gln Asp Asn Lys Arg Gly His
210 215
Claims (12)
- 치료에 사용하기 위한 단리된 펩티드로서, 상기 펩티드는 B군 스트렙토코커스로부터 얻을 수 있는 서열 SEQ ID No. 23으로 정의된 아미노산 서열을 가지는 펩티드.
- 삭제
- 치료에 사용하기 위한, 제 1항에 따른 펩티드를 코드하는 폴리뉴클레오티드.
- 삭제
- 제 1항에 따른 펩티드를 포함하는 백신.
- 제 1항 또는 제 3항에 따른 생성물을 이용하여 잠재적 항균제를 선별하는 방법.
- 제 1항에 따른 펩티드에 대항하여 배양된 항체.
- 제 1항 또는 제 3항에 따른 생성물을 포함하는, 세균성 감염과 관련된 질병의 치료 또는 예방에 사용하기 위한 약제.
- 제 8항에 있어서, 상기 감염이 B군 스트렙토코커스 감염인 약제.
- 제 8항에 있어서, 상기 감염이 병소 감염인 약제.
- 제 8항에 있어서, 상기 감염이 요로 감염인 약제.
- SEQ ID No. 23으로 정의된 서열에 특이적으로 결합하는 항체.
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KR1020070098153A KR20070101197A (ko) | 1998-12-22 | 2007-09-28 | 유전자와 단백질들, 및 그들의 사용 |
KR1020080043336A KR20080050550A (ko) | 1998-12-22 | 2008-05-09 | 유전자와 단백질들, 및 그들의 사용 |
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KR1020080043336A KR20080050550A (ko) | 1998-12-22 | 2008-05-09 | 유전자와 단백질들, 및 그들의 사용 |
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EP (3) | EP2105504A3 (ko) |
JP (1) | JP2002533083A (ko) |
KR (3) | KR100790653B1 (ko) |
CN (1) | CN101066447A (ko) |
AP (1) | AP1502A (ko) |
AT (1) | ATE353367T1 (ko) |
AU (1) | AU776735B2 (ko) |
CA (1) | CA2354135A1 (ko) |
CY (1) | CY1106559T1 (ko) |
CZ (1) | CZ20012172A3 (ko) |
DK (1) | DK1141308T3 (ko) |
EA (1) | EA004444B1 (ko) |
ES (1) | ES2281977T3 (ko) |
HK (1) | HK1039353A1 (ko) |
HU (1) | HUP0104825A3 (ko) |
NO (1) | NO20013102L (ko) |
NZ (3) | NZ512297A (ko) |
OA (1) | OA11734A (ko) |
PL (1) | PL201887B1 (ko) |
PT (1) | PT1141308E (ko) |
SI (1) | SI1141308T1 (ko) |
WO (1) | WO2000037646A2 (ko) |
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US6890539B2 (en) * | 1998-12-22 | 2005-05-10 | Microscience, Ltd. | Genes and proteins, and their use |
SI1141308T1 (sl) * | 1998-12-22 | 2007-08-31 | Microscience Ltd | Streptokokni proteini skupine B in njihova uporaba |
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CN106822885B (zh) | 2017-02-16 | 2020-06-30 | 清华大学 | 肺炎链球菌疫苗 |
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1999
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- 1999-12-22 EP EP09159100A patent/EP2105504A3/en not_active Withdrawn
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- 1999-12-22 KR KR1020017007911A patent/KR100790653B1/ko not_active IP Right Cessation
- 1999-12-22 ES ES99962422T patent/ES2281977T3/es not_active Expired - Lifetime
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- 1999-12-22 PL PL349320A patent/PL201887B1/pl not_active IP Right Cessation
- 1999-12-22 AT AT99962422T patent/ATE353367T1/de not_active IP Right Cessation
- 1999-12-22 US US09/868,352 patent/US6812021B1/en not_active Expired - Fee Related
- 1999-12-22 EP EP99962422A patent/EP1141308B1/en not_active Expired - Lifetime
- 1999-12-22 EA EA200100700A patent/EA004444B1/ru not_active IP Right Cessation
- 1999-12-22 CN CNA2007101018407A patent/CN101066447A/zh active Pending
- 1999-12-22 CA CA002354135A patent/CA2354135A1/en not_active Abandoned
- 1999-12-22 AU AU18780/00A patent/AU776735B2/en not_active Ceased
- 1999-12-22 JP JP2000589700A patent/JP2002533083A/ja active Pending
- 1999-12-22 AP APAP/P/2001/002189A patent/AP1502A/en active
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-
2001
- 2001-06-21 NO NO20013102A patent/NO20013102L/no not_active Application Discontinuation
- 2001-12-20 HK HK01108928A patent/HK1039353A1/xx unknown
-
2004
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-
2007
- 2007-05-04 CY CY20071100589T patent/CY1106559T1/el unknown
- 2007-08-17 US US11/892,024 patent/US20090274717A1/en not_active Abandoned
- 2007-09-28 KR KR1020070098153A patent/KR20070101197A/ko not_active Application Discontinuation
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2008
- 2008-05-09 KR KR1020080043336A patent/KR20080050550A/ko not_active Application Discontinuation
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