JP2019514439A - 抗細菌ポリペプチドの最小発育阻止濃度を評価および決定するための微量液体希釈方法 - Google Patents
抗細菌ポリペプチドの最小発育阻止濃度を評価および決定するための微量液体希釈方法 Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/18—Testing for antimicrobial activity of a material
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01017—Lysozyme (3.2.1.17)
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Toxicology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Enzymes And Modification Thereof (AREA)
Abstract
Description
例1
異なる動物血清(5〜50%)−イヌ、ウサギ、ウマ、マウス血清
溶血(Laked)ウマ血液(1〜5%)
DTT(0.05〜5mM)
動物血清(5〜50%)+DTT(0.5mM)
Tween 80(0.002%)
BSA(0.05〜0.5%)
NaCl(1〜5%)
BSA 0.1%、NaCl 2%、200rpm2で撹拌
BSA 0.1%、NaCl 2%
CaCl2(50μg/mlまで)
MgCl2(50μg/mlまで)
CaCl2(50μg/mlまで)+MgCl2(50μg/mlまで)
TCEP(0.01〜5mM)
種々のブロスおよび培地−LB、TSB、BHI、1/4MHB、1/2MHB
pH、接種材料および大気のバリエーション
2人の異なる個人が実施した連続5日間の分析
ウマ血清の種々の供給源(Sigma、Corning、Gibco、BioreclamationIVT、Mediatech、RAMBIO、ATCC、Central Biomedia、Lampire)
粉末CA−MHB/MHB II(BDおよびSigma)および予め作製された液体MHB II(BDおよびTeknova)の各々の種々の供給源
DTTの複数の供給源(Sigma(液体、粉末)、G−Biosciences)
周囲空気中で30〜37℃の発育温度、5%CO2中37℃、最大で200rpmのプレート撹拌
7.4±0.6の最終/最適な培地pH範囲を決定した。
5×105±1−log10の最終/最適な接種材料(CFU/ml)範囲
ブロス−微量希釈感受性試験を実施するための一般的手順が、このセクションに提供される。この手順は、CLSI方法論(文書M07−A9、2015)のバリエーションであり、高度に荷電した抗菌ペプチドのMICを試験するための、Wiegandら、2008(非特許文献35)(付録D、セクションD1を参照のこと)によって記載された方法に基づく。
1.24℃の水浴中で5分間の懸濁によって、凍結溶解素ポリペプチド(例えば、CF−301)ストック溶液を解凍する。解凍した試料を、使用まで、氷上で30分以下で貯蔵する。未使用のポリペプチド(CF−301)を廃棄する。
2.アッセイに必要な所望の2倍溶解素ポリペプチド(例えば、CF−301)希釈範囲を決定する。ほとんどの黄色ブドウ球菌株について、この範囲は、8または16μg/mlの所望の最終濃度で開始する。一部のバンコマイシン中等度耐性黄色ブドウ球菌株について、この範囲は、512μg/mlで開始する。
3.各希釈について所望の最終濃度の2倍で溶解素ポリペプチド(例えば、CF−301)マスター希釈ストックを調製し、カラム1〜10の適切なウェルに0.05mlを満たす。0.1mlのブロスを、無菌性対照として機能するようにカラム12のウェル中にピペッティングし、0.05mlを、発育対照として機能するようにカラム11のウェル中にピペッティングする。
1.18〜24時間の血液寒天プレートから選択される単離されたコロニーの直接的ブロス懸濁を行うことによって、接種材料を調製する。ブロス懸濁は、BBL(商標)ミューラー・ヒントンブロス、2mlチューブ(BD Diagnostic Systems、カタログ番号296164)中で実施され得る。
2.Grant InstrumentsのDEN−1デンシトメーターを使用して、0.5マクファーランド標準と等価な濁度を達成するように懸濁物を調整する。
3.調製の15分以内に、調整された接種材料をブロス中に希釈し、そうして、接種の後、各ウェルは、およそ5×105CFU/mlの最終濃度を含む。カラム1〜11の各ウェルについての接種材料体積は0.05mlになるので、0.5マクファーランドの懸濁物は、1×106CFU/mlにするために1:100に希釈すべきである。0.05mlのこの懸濁物をマイクロタイタープレートウェル(既に0.05mlを含有している)中に接種する場合、細菌の最終試験濃度は、およそ5×105CFU/mlである。
4.接種材料を上記のように標準化した後15分以内に、カラム1〜11の各ウェルに、0.05mlを接種する。各ウェルの最終体積は、ここで0.1mlである。
5.同時インキュベーションのために血液寒天プレート上にアリコートを継代培養することによって、接種材料懸濁物の純度チェックを実施する。
1.CF−301を含有するウェルにおける発育の量を、発育対照ウェルにおける発育の量と比較する。試験が有効であるとみなされるには、許容可能な発育が発育対照ウェル中で起きることが必要である。目視でMIC値を決定する。
2.独立した記録として、Molecular Devices SpectraMax M3プレートリーダーで決定した各トレイのウェルについてのOD600値を読み取り、保存する。
補充物
粉末からのDL−ジチオスレイトール(DTT)ストック溶液(1M)
1.1.5gのDTTを1ml H2O(UltraPure DNase/RNaseフリー蒸留水)中に溶解させる
2.体積を蒸留水で10mlにし、0.22μmフィルターを通過させることによって滅菌する
3.使用の当日に調製する(貯蔵および再使用しない)
DL−ジチオスレイトール(DTT)溶液(H2O中1M)
1.ガラスバイアルを無菌的に開封し、適切な量を分配する
2.使用の当日に調製する(貯蔵および再使用しない)
ウマ血清(100%)
1.4℃で一晩または24℃で1時間を超えるインキュベーションのいずれかによって、凍結ウマ血清を解凍する
2.オートクレーブして冷却したMHB IIブロスに、適切な量の血清を無菌的に添加する
3.50mlアリコートで−20℃で凍結貯蔵する
5%ヒツジ血液を含むトリプシンダイズ寒天
市販の供給源から、予め作製されたトリプシン・ダイズ寒天プレート(5%ヒツジ血液を補充した)を得る
カチオン調整されたミューラー・ヒントンブロス
市販の供給源から、脱水ミューラー・ヒントンIIブロス(カチオン調整された)を得る。
この形態は、20〜25mgのCa2+/Lおよび10〜12.5mgのMg2+/Lを含有しなければならない。
1.製造業者の推奨に正確に従って、MHB IIを調製し、オートクレーブし、1時間かけて55℃まで冷却し、0.22μmメンブレンを通過させることによって濾過滅菌し、2〜8℃で一晩冷やす。
2.pHをチェックする。最終pHは、7.2〜7.4でなければならない。
3.1週間以下にわたって、光から保護して2〜8℃で貯蔵する。
25%ウマ血清および0.5mM DTTを含む、カチオン調整されたミューラー・ヒントンブロス
1.セクションB3.1に記載されるように、カチオン調整されたミューラー・ヒントンブロスを調製する。
2.ブロスを2〜8℃で一晩冷やした後、必要とされる各100mlのために、25mlのウマ血液を75mlのブロスに添加する。ウマ血液の調製についてはセクションB1.2を参照のこと。
3.穏やかに旋回させて混合する。
4.混合した後、必要とされる各100mlのブロス+25%ウマ血清のために、0.05mlの1M DTTストック溶液を添加する。DTTの供給源に依存して、調製についてセクションB1.1またはB1.2を参照のこと。
5.最終pHは、7.4でなければならない。
6.使用の当日にのみ新鮮な培地を調製する。培地は貯蔵および再使用しない。
細菌発育培地
BBL(商標)ミューラー・ヒントンIIブロス、カチオン調整、オートクレーブによって滅菌済み(BD Diagnostics、カタログ番号212322、ロット番号5257869、有効期限2019年5月31日)
ミューラー・ヒントンブロス2、カチオン調整、オートクレーブによって滅菌済み(Sigma−Aldrich、カタログ番号90922、ロット番号BCBR3303V、有効期限2020年11月)
BBL(商標)ミューラー・ヒントンIIブロス、カチオン調整、400ml、無菌(BD Diagnostics、カタログ番号297963、ロット番号6014547、有効期限2017年1月12日)
ミューラー・ヒントンIIブロス、カチオン調整、1000mL、無菌(Teknova、カタログ番号M5860、ロット番号M586012B1601、有効期限2016年12月9日)
Trypticase(商標)ダイズ寒天プレート、5%ヒツジ血液を含む(TSA II)(BD Diagnostics、カタログ番号221239、ロット番号6049996、有効期限2016年6月10日)
ウマ血清、ドナー群、濾過滅菌済み(Sigma−Aldrich、カタログ番号H1270、ロット番号15G382、有効期限2016年6月、−20℃で凍結貯蔵)
ウマ血清、濾過滅菌済み(BioreclamationIVT、カタログ番号HSESRM、ロット番号HSE1225、有効期限2016年10月、−20℃で凍結貯蔵)
ウマ血清、ニュージーランド起源、ドナー群、濾過滅菌済み(Gibco、カタログ番号16050−122、ロット番号1671315、有効期限2019年2月、−20℃で凍結貯蔵)
ドナーウマ血清、米国から調達、濾過滅菌済み(Corning、カタログ番号35−030−CV、ロット番号35030105、有効期限2018年7月、−20℃で凍結貯蔵)
ドナーウマ血清、米国から調達、濾過滅菌済み(Sigma−Aldrich、カタログ番号12449C、ロット番号14A277、2018年2月28日、−20℃で凍結貯蔵)
ヒト雄性AB血漿由来のヒト血清、米国起源、濾過滅菌済み(Sigma−Aldrich、カタログ番号SLBN4664V、有効期限2018年4月、−20℃で凍結貯蔵)
プールされた正常ヒト雄性AB血清、濾過滅菌済み(Innovative Research Inc.、カタログ番号IPLA−SERAB、ロット番号19799、−20℃で凍結貯蔵)
プールされた正常ヒト雄性血漿、クエン酸NA抗凝固剤、濾過滅菌済み(Innovative Research Inc.、カタログ番号IPLA−N、ロット番号18944、−20℃で凍結貯蔵)
ウサギ血清、米国起源、濾過滅菌済み(Sigma−Aldrich、カタログ番号R7136、ロット番号13E108、有効期限2017年5月、−20℃で凍結貯蔵)
イノベーティブグレードの米国起源ビーグル血清(Innovative Research Inc.、カタログ番号IBG−SER、ロット番号17654、有効期限2018年6月、−20℃で貯蔵)
Remel(商標)溶血ウマ血液(Thermo Scientific、カタログ番号R54072、−20℃で凍結貯蔵)
DL−ジチオスレイトール溶液、H2O中1M(Sigma−Aldrich、カタログ番号646563−10X.5ML、ロット番号MKBW5575V、24℃で未開封貯蔵)
DL−ジチオスレイトールBioUltra、分子生物学用、≧99.5%(RT)(Sigma−Aldrich、カタログ番号43815−25G、ロット番号BCBBD7009V、2〜8℃で貯蔵)
DL−ジチオスレイトール(G−Biosciences、カタログ番号RC−046、ロット番号151106、2〜8℃で貯蔵)
トリス(2−カルボキシエチル)ホスフィン塩酸塩溶液、0.5M、pH7.0(Sigma−Aldrich、カタログ番号646547−10X1ML、ロット番号MKBW8503V、24℃で未開封貯蔵)
TWEEN(登録商標)80(Sigma−Aldrich、カタログ番号P4780−100ML、ロット番号MKBW2896V、24℃で貯蔵)
塩化ナトリウム(NaCl)(Fisher BioReagents、カタログ番号BP358−10、ロット番号150661、24℃で貯蔵)
塩化カルシウム(Fisher Bioreagents、カタログ番号C77−212、ロット番号110651、24℃で貯蔵)
塩化マグネシウム、無水物、≧98%(Sigma−Aldrich、カタログ番号M8266−100G、ロット番号120M0094V、24℃で貯蔵)
ウシ血清アルブミン、凍結乾燥粉末、≧96%(Sigma−Aldrich、カタログ番号A2153、ロット番号SLBL5462V、2〜8℃で貯蔵)
Falcon(登録商標)96ウェル細胞培養プレート、ポリスチレン、無菌、u底、低蒸発蓋(Corning、カタログ番号351177、ロット番号6026023)
BBL(商標)ミューラー・ヒントンブロス、2mlチューブ(BD Diagnostic Systems、カタログ番号296164、ロット番号6054984)
DEN−1ベンチトップデンシトメーター(Grant Biosciences、カタログ番号DEN−1、ロット番号050102−1111−0426)
SpectraMax M3マルチモードマイクロプレートリーダー(Molecular Devices Inc.)
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Claims (15)
- 動物血清および還元剤を補充したブロス中で抗細菌ペプチドを評価することを含む、グラム陽性細菌の微量液体希釈(BMD)感受性試験のための方法。
- ブロスに、10%動物血清から50%動物血清の間の濃度で動物血清が補充される、請求項1に記載の方法。
- ブロスに、10%動物血清から30%動物血清の間の濃度で動物血清が補充される、請求項1に記載の方法。
- ブロスに、15%動物血清から30%動物血清の間の濃度で動物血清が補充される、請求項1に記載の方法。
- ブロスに、20%動物血清から30%動物血清の間の濃度で動物血清が補充される、請求項1に記載の方法。
- ブロスに、20%ウマ血清から30%ウマ血清の間の濃度でウマ血清が補充される、請求項1に記載の方法。
- ブロスが、カチオン調整されたブロスである、請求項1に記載の方法。
- ブロスが、ミューラー・ヒントンブロス(MHB)である、請求項1に記載の方法。
- 還元剤が、ジチオスレイトール(DTT)およびトリス(2−カルボキシエチル)ホスフィン塩酸塩(TCEP)から選択される、請求項1に記載の方法。
- 還元剤の量が、0.1mMから1mMの間である、請求項1に記載の方法。
- 還元剤の量が、0.25mMから1mMの間である、請求項1に記載の方法。
- 抗細菌ペプチドが溶解素ポリペプチドである、請求項1に記載の方法。
- 溶解素ポリペプチドが、グラム陽性細菌を死滅させるのに有効なPlySs2(CF−301)またはそのバリアントもしくは誘導体である、請求項1に記載の方法。
- 溶解素ポリペプチドである抗細菌ペプチドを含み、1種または複数の抗細菌剤をさらに含む組成物を評価するための、請求項1に記載の方法。
- 1種または複数の抗細菌剤が抗生物質である、請求項14に記載の方法。
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ES2767294T3 (es) * | 2014-06-26 | 2020-06-17 | Univ Rockefeller | Lisinas de Acinetobacter |
WO2019165454A1 (en) * | 2018-02-26 | 2019-08-29 | Contrafect Corporation | Modified plyss2 lysins and uses thereof |
EP3820605A4 (en) | 2018-07-11 | 2022-02-23 | Selux Diagnostics Inc. | ASSAYS AND REAGENTS FOR TESTING FOR ANTIBIOTIC SENSITIVITY |
WO2020198073A1 (en) * | 2019-03-22 | 2020-10-01 | Contrafect Corporation | Method of treating infective endocarditis |
CA3136461A1 (en) * | 2019-04-11 | 2020-10-15 | Contrafect Corporation | Method of treating and preventing bone and joint infections |
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JP2837846B2 (ja) | 1986-10-08 | 1998-12-16 | バーンスタイン,デビッド | グループa連鎖球菌抗原を露出させる方法およびグループa連鎖球菌を同定するための改善された診断試験 |
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CN109152822B (zh) | 2023-12-05 |
EP3454888A4 (en) | 2019-12-11 |
IL262844A (en) | 2018-12-31 |
EP3454888A1 (en) | 2019-03-20 |
CA3023730A1 (en) | 2017-11-16 |
RU2018135238A3 (ja) | 2020-09-11 |
AU2017263563A1 (en) | 2018-10-18 |
US20190106724A1 (en) | 2019-04-11 |
EP3454888B1 (en) | 2021-02-24 |
DK3454888T3 (da) | 2021-04-26 |
US10851401B2 (en) | 2020-12-01 |
MX2018013372A (es) | 2019-05-09 |
BR112018073205A2 (pt) | 2019-02-19 |
ZA201806685B (en) | 2021-02-24 |
IL262844B2 (en) | 2023-07-01 |
JP6875756B2 (ja) | 2021-05-26 |
CN109152822A (zh) | 2019-01-04 |
RU2018135238A (ru) | 2020-06-15 |
IL262844B1 (en) | 2023-03-01 |
KR20190004799A (ko) | 2019-01-14 |
WO2017197227A1 (en) | 2017-11-16 |
RU2754667C2 (ru) | 2021-09-06 |
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