JP2013532955A - バイオフィルムの低減方法 - Google Patents
バイオフィルムの低減方法 Download PDFInfo
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- JP2013532955A JP2013532955A JP2013506649A JP2013506649A JP2013532955A JP 2013532955 A JP2013532955 A JP 2013532955A JP 2013506649 A JP2013506649 A JP 2013506649A JP 2013506649 A JP2013506649 A JP 2013506649A JP 2013532955 A JP2013532955 A JP 2013532955A
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- endolysin
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Abstract
【選択図】図1
Description
a)膜破壊活性またはLPS破壊活性を有するペプチドが融合された、グラム陰性菌および/またはグラム陽性菌の細胞壁の分解活性を有する酵素を含む融合タンパク質を提供し;
b)前記融合タンパク質と物質、液体、表面または生体物質とを接触させる
段階を含む前記方法に関する。
c)膜破壊活性またはLPS破壊活性を有するペプチドが融合されたエンドリシン、オートリシンまたはバクテリオシンを含む融合タンパク質を提供し;
d)前記融合タンパク質と物質、液体、表面または生体物質とを接触させる
段階を含む前記方法に関する。
表2:
表3:
表4:
配列番号1に示したphiKZgp144および配列番号2に示したELgp188は、N末端ペプチドグリカン結合ドメインおよびC末端触媒ドメインを有するシュードモナス・エルギノーサファージφKZおよびEL由来のモジュラーエンドリシンである(Briersら、2007)。
対数的に増殖している(〜106/ml)P.エルギノーサPAO1p細胞(Pirnay JP et al. (2003), J Clin Microbiol., 41(3):1192-1202)を100倍希釈し(最終密度は〜106/ml)、緩衝液(20mM NaH2P04-NaOH pH7.4;0.5M NaCl;0.5Mイミダゾール)中、100μg/mlの最終濃度で、各10μgの未透析タンパク質(未修飾エンドリシン、phiKZgp144(配列番号1)およびELpg188(配列番号2)ならびに修飾エンドリシンバリアント、POLY-gp144(配列番号35)、(POLY)2-gp144(配列番号36)、POLY-gp188(配列番号39)および(POLY)2-gp188(配列番号40)と共に室温でインキュベートした。1時間後、細胞浮遊液をPBS緩衝液で希釈し(10e-5、10e-4および10e-3)、プレーティングした(標準LB培地、終夜37℃でインキュベートした)。さらに、PBS緩衝液中に細胞を含む陰性対照をプレーティングした。終夜インキュベーション後に、残存コロニーを計測した。計測細胞数に基づいて、相対的不活化(%)(=100-(Ni/No)*l00:N0=未処理細胞数;Ni=処理細胞数)として対数単位(=log10N0/Ni)で抗菌活性を算出した(表6)。すべての試料を6連で行った。平均値/標準偏差を示す。スチューデントt検定を用いて統計解析を行った。
POLY-gp144(配列番号35)をコードするオープンリーディングフレームをpPICZαAシャトルベクター(Invitrogen社)にクローニングし、続いてこれを相同組換えによってP.パストリス(P.pastoris)のゲノムに組み込んだ(製造業者の指示に従って;P.パストリスX33細胞、Invitrogen社)。BMMY培地中でメタノール(1%)によって遺伝子発現を誘導し、1、3および4日後に酵素活性の存在に関して上清を分析した。そのために、P.パストリス発現培養物30μl量の上清を、クロロホルムで透過化させたP.エルギノーサPAO1p細胞(Pirnay JP et al. (2003), J Clin Microbiol., 41(3):1192-1202) 270μlに、1、3および4日後に加えた(緩衝液条件:KH2PO4/K2HP04 I=120mM pH6.2)。続いて、分光光度学的に吸光度を記録した(図2)。吸光度の低下は、P.パストリスによる溶菌酵素の分泌を示す。陰性対照として、発現プラスミドを含まないP.パストリスX33を含めた。このように、上清試料の添加による基質の溶解は、P.パストリスによるPOLY-gp144(配列番号35)の組換え産生および分泌の成功の尺度である。1日後、わずかな酵素活性を検出できた。最大活性は3日後に観察された。なぜなら、4日後に上清における活性の有意な増加が観察されなかったからである。P.パストリスの細胞密度に対する毒作用は認められなかった。
ポリカチオン性ペプチドの潜在能を試験および比較するために、タンパク質のN末端に異なるポリカチオン性ペプチドを有するphiKZgp144および他のエンドリシンのバリアントをコードする遺伝子を合成した。ペプチドの変化は、リンカー配列の長さ、組成および挿入に関する。一方では、N末端KRKモチーフ複数体を有するさらなるポリカチオン性ペプチドを産生させた。他方では、アルギニン(R)またはリジン(K)のみからなるポリカチオン性ペプチドを産生させた。さらに、長いポリカチオン性ペプチドの翻訳を促進するために、リンカー配列を含むポリカチオン性ペプチドを産生させた。
配列番号8のPSP3gp10は、サルモネラ・ティフィムリウムファージPSP3に由来する165アミノ酸残基の球状エンドリシンであり、λ様ムラミダーゼ触媒ドメインを有する。BLASTpおよびPfam分析によって予測されるように、PSP3gp10エンドリシンは、アミノ酸残基約34〜アミノ酸残基約152の範囲にその触媒ドメインを含む。
1.流速0.5ml/分での、洗浄緩衝液(60mMイミダゾール、0.5mM NaClおよび20mM NaH2P04-NaOH pH7.4)10カラム体積を用いるHistrap HP 1mlカラム(GE HEALTHCARE社)の平衡化。
2.流速0.5ml/分での、Histrap HP 1mlカラムへの全溶解物(所望のエンドリシンを有する)のローディング。
3.流速1ml/分での、洗浄緩衝液15カラム体積を用いるカラムの洗浄。
4.流速0.5ml/分での、溶出緩衝液(500mMイミダゾール、5mM NaClおよび20mM NaH2P04-NaOH pH7.4)10カラム体積を用いる、カラムからの結合エンドリシンの溶離。
*Pirnay JP et al. (2003). Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone. J Clin Microbiol., 41(3):1192-1202.
配列番号9のP2gp09は、エシェリキア・コリファージP2に由来する165アミノ酸残基の球状エンドリシンであり、λ様ムラミダーゼ触媒ドメインを有する。BLASTpおよびPfam分析によって予測されるように、P2gp09エンドリシンは、アミノ酸残基約34〜アミノ酸残基約152の範囲にその触媒ドメインを含む。
1.流速0.5ml/分での、洗浄緩衝液(60mMイミダゾール、0.5mM NaClおよび20mM NaH2P04-NaOH pH7.4)10カラム体積を用いるHistrap HP 1mlカラム(GE HEALTHCARE社)の平衡化。
2.流速0.5ml/分での、Histrap HP 1mlカラムへの全溶解物(所望のエンドリシンを有する)のローディング。
3.流速1ml/分での、洗浄緩衝液15カラム体積を用いるカラムの洗浄。
4.流速0.5ml/分での、溶出緩衝液(500mMイミダゾール、5mM NaClおよび20mM NaH2P04-NaOH pH7.4)10カラム体積を用いる、カラムからの結合エンドリシンの溶離。
*Pirnay JP et al., (2003). Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone. J Clin Microbiol., 41(3):1192-1202.
配列番号7のOBPgpLYSは、推定上のN末端ペプチドグリカン結合ドメインおよびC末端触媒キチナーゼドメインを有するシュードモナス・プチダファージOBPに由来する328アミノ酸残基のモジュラーエンドリシンである。BLASTpおよびPfam分析によって予測されるように、OBPgpLYSエンドリシンは、アミノ酸残基約126〜アミノ酸残基約292の範囲にその触媒ドメインを含み、アミノ酸残基約7〜96の範囲にN末端ペプチドグリカン結合ドメインを含む。
1.流速0.5ml/分での、洗浄緩衝液(60mMイミダゾール、0.5mM NaClおよび20mM NaH2P04-NaOH pH7.4)10カラム体積を用いるHistrap HP 1mlカラム(GE HEALTHCARE社)の平衡化。
2.流速0.5ml/分での、Histrap HP 1mlカラムへの全溶解物(所望のエンドリシンを有する)のローディング。
3.流速1ml/分での、洗浄緩衝液15カラム体積を用いるカラムの洗浄。
4.流速0.5ml/分での、溶出緩衝液(500mMイミダゾール、5mM NaClおよび20mM NaH2P04-NaOH pH7.4)10カラム体積を用いる、カラムからの結合エンドリシンの溶離。
*Pirnay JP, De Vos D, Cochez C, Bilocq F, Pirson J, Struelens M, Duinslaeger L, Cornelis P, Zizi M, Vanderkelen A. (2003). Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone. J Clin Microbiol., 41(3):1192-1202.
未修飾および修飾エンドリシンの抗菌活性に対するEDTAの影響を測定するために、異なる濃度のEDTAおよびエンドリシンを用いて、シュードモナス・エルギノーサPAO1p細胞(Pirnay JP et al. J Clin Microbiol., 41(3):1192-1202 (2003))に対して未修飾OBPgpLYSエンドリシン(配列番号7)およびPKOBPgpLYSエンドリシン(配列番号61)の抗菌活性を試験した。対数的に増殖している細菌細胞(0.6のOD600nm)を100倍希釈して最終密度約106/mlにし、未修飾エンドリシンOBPgpLYS(配列番号7)および修飾エンドリシンPKOBPgpLYS(配列番号61)と共に30分間室温で振盪なしでインキュベートした。インキュベーションのために、各エンドリシンを、緩衝液(20mM NaH2P04-NaOH pH7.4;0.5M NaCl;0.5Mイミダゾール)中、エンドリシンの最終濃度0.013μM、0.131μMおよび1.315μMで用いた。それに関して、以下の異なるEDTA濃度:0mM、0.05mM、0.5mMおよび10mMを用いた。対照として、エンドリシンを加えないで、代わりに緩衝液(20mM NaH2P04-NaOH pH7.4;0.5M NaCl;0.5Mイミダゾール)を加えた試料1つもまた30分間インキュベートした。インキュベーション後、細胞浮遊液を3回希釈し(それぞれ105-104-103細胞/ml)、各希釈液100μlをLB培地上にプレーティングした。37℃での終夜インキュベーション後に残存コロニーを計測した。計測細胞数に基づいて、対数単位での相対的不活化(=log10N0/Ni:N0=未処理細胞数;Ni=処理細胞数、共にインキュベーション後に計測した)として抗菌活性を算出した(表17)。すべての試料を3連で行った。平均値+/-標準偏差を示す。観察される最大減少(5.69対数単位)は、10細胞/mlの検出レベルおよび最初の細胞密度に依存する。“Δ”は、OBPgpLYSおよびPKOBPgpLYS試料それぞれの間の活性の差異を示す。
ポリカチオン性ペプチドphiKZgp144および他のエンドリシンのバリアントの潜在能を試験し、比較するために、タンパク質のN末端にポリカチオン性ペプチドを有するコード遺伝子を合成した。
本実験において、シュードモナス・エルギノーサ2572株および2573株のバイオフィルムに対する修飾エンドリシンバリアントSMAP29-KZ144およびPK-OBPならびにエンドリシンOBPおよびKZ144ならびにペプチドPKの抗菌活性を試験した。
シュードモナス・エルギノーサ2572のムコイド株(患者分離株)、シュードモナス・エルギノーサ2573ならびに非ムコイドE.コリBL21(DE3)の終夜液体培養物をOD600=0.1まで希釈した。ポリスチレン96ウェルプレートに培養物100μl/ウェルで接種した。37℃でのインキュベーション4時間後、上清を捨て、付着細菌を生理食塩水(PS)100μlを用いて洗浄した。接種したウェルに液体LB培地100μlを充填し、さらに24時間インキュベートした。上清を捨てた後、発達したバイオフィルムをPS100μlで再度洗浄した。
50μg/ウェルのPKKZ144または20u/ウェルのアルギン酸リアーゼまたは50μg/ウェルのSMAP29-KZ144およびKZ144または25μg/ウェルのPK-OBPおよびOBPまたは1,25μgのPK-ペプチド(すべて500mM NaClを含む緩衝液中)1部に対して2xLB(NaClなし)培地1部で希釈して用いてバイオフィルムを処理し、12時間インキュベートした。未処理のシリーズを陰性対照として行った(タンパク質緩衝液1部に対して2xLB(NaClなし)1部)。上清を捨てた後、発達したバイオフィルムをPS100μlで再度洗浄した。
洗浄したバイオフィルムをメタノール300μlで固定し(99%;15分)、風乾した。0.3%クリスタルバイオレット100μlを用いて染色を行った。20分後、ウェルを水道水ですすぎ、33%酢酸300μlを用いて、バイオフィルムの細胞外マトリックスから結合クリスタルバイオレットを溶解した。20分後、1:10希釈を行って、吸収(590nm)を測定した。
本実験において、アシネトバクター・バウマニーDSMZ30007株のバイオフィルムに対して、修飾エンドリシンバリアントPK-OBP、エンドリシンOBPおよびペプチドPKの抗菌活性を試験した。
本実験において、スタフィロコッカス・アウレウスKS13株のバイオフィルムに対するPly2638-PKおよびPK-リゾスタフィンの融合タンパク質、酵素リゾスタフィンおよびPly2638ならびにペプチドPKの抗菌活性を試験した。
本実験において、リステリア・モノサイトゲネスScottA株のバイオフィルムに対して、修飾エンドリシンバリアントペンタペプチド-Ply511の抗菌活性を試験した。
Claims (18)
- 細菌性バイオフィルムの除去、低減または予防方法であって、
a)膜破壊活性またはLPS破壊活性を有するペプチドが融合されたエンドリシン、オートリシンまたはバクテリオシンを含む融合タンパク質を提供し;
b)前記融合タンパク質と物質、液体、表面または生体物質とを接触させる
ことを含む前記方法。 - エンドリシン、オートリシンまたはバクテリオシンに融合される前記ペプチドが、長さ6〜39アミノ酸残基を有する合成または天然に存在するペプチドである、請求項1に記載の方法。
- エンドリシン、オートリシンまたはバクテリオシンに融合される前記ペプチドが、合成カチオン性、合成ポリカチオン性、合成疎水性、合成両親媒性または天然に存在する抗菌ペプチドである、請求項1または2に記載の方法。
- 前記ペプチドが、エンドリシン、オートリシンまたはバクテリオシンのN末端および/またはC末端に融合され、特にエンドリシン、オートリシンまたはバクテリオシンのN末端に融合される、請求項1〜3のいずれか1つに記載の方法。
- 前記エンドリシン、オートリシンまたはバクテリオシンが、グラム陰性菌および/またはグラム陽性菌の細胞壁の分解活性、特に腸内細菌科(エシェリキア属、特にE.コリ、サルモネラ属、シゲラ属、シトロバクター属、エドワージエラ属、エンテロバクター属、ハフニア属、クレブシエラ属、特にK.ニューモニエ、モルガネラ属、プロテウス属、プロビデンシア属、セラチア属、エルシニア属)、シュードモナス科(シュードモナス属、特にP.エルギノーサ、バークホルデリア、ステノトロホモナス属、シュワネラ属、スフィンゴモナス属、コマモナス属)、ナイセリア属、モラクセラ属、ビブリオ属、アエロモナス属、ブルセラ属、フランシセラ属、ボルデテラ属、レジオネラ属、バルトネラ属、コクシエラ属、ヘモフィルス属、パスツレラ属、マンヘミア属、アクチノバチルス属、ガードネレラ属、スピロヘータ科(トレポネーマ属およびボレリア属)、レプトスピラ科、カンピロバクター属、ヘリコバクター属、スピリルム属、ストレプトバチルス属、バクテロイデス科(バクテロイデス属、フソバクテリウム属、プレボテラ属、ポルフィロモナス属)、アシネトバクター属、特にA.バウマニからなる群から選択されるグラム陰性菌の細胞壁の分解活性を有し、ここでグラム陽性菌が、リステリア・モノサイトゲネス、スタフィロコッカス・アウレウス、エンテロコッカス・フェカリス、エンテロコッカス・フェシウム、ストレプトコッカス・ニューモニエ、ストレプトコッカス・ピオゲネス、ストレプトコッカス・ミュータンス、ストレプトコッカス・エクイ、クロストリジウム・ディフィシル、クロストリジウム・ボツリヌム、クロストリジウム・テタニ、クロストリジウム・パーフリンジェンス、バチルス・アンスラシス、バチルス・セレウス、プロピオニバクテリウム・アクネス、マイコバクテリウム・アビウム、マイコバクテリウム・ツベルクローシス、コリネバクテリウム・ジフテリエ、マイコプラズマ・ニューモニエ、アクチノミセス属からなる群から選択される、請求項1〜4のいずれか1つに記載の方法。
- 前記エンドリシンが、配列番号1のphiKZgp144、配列番号2のELgp188、配列番号3のサルモネラエンドリシン、配列番号4の腸内細菌ファージT4エンドリシン、配列番号5のアシネトバクター・バウマニーエンドリシン、配列番号6のE.コリファージK1Fエンドリシン、配列番号7のOBPgpLys、配列番号8のPSP3サルモネラエンドリシン、配列番号9のE.コリファージP2エンドリシン、配列番号85のPly511、配列番号92のPly2638からなる群から選択されるかまたは、前記バクテリオシンが配列番号87である、請求項1〜5のいずれか1つに記載の方法。
- カチオン性/ポリカチオン性ペプチドが配列番号10〜30および32〜34のアミノ酸配列を示すか、または抗菌ペプチドが配列番号93〜133のアミノ酸配列を示すか、または疎水性ペプチドが配列番号134および135のアミノ酸配列を示すか、または両親媒性ペプチドが配列番号136〜138のアミノ酸配列を示す、請求項1〜6のいずれか1つに記載の方法。
- 前記エンドリシンバリアントまたはバクテリオシンバリアントが、配列番号35〜49、53、57、62〜64、66〜78および139〜142からなる群から選択されるアミノ酸配列を含む、請求項1〜7のいずれか1つに記載の方法。
- 融合タンパク質に接触する物質が、石、岩、土壌、堆積物、食物、飼料または化粧品である、請求項1〜8のいずれか1つに記載の方法。
- 融合タンパク質に接触する液体が、水、特に飲料水、地下水もしくは廃水、熱水泉、海、湖、川、任意の種類の水性系、コンタクトレンズ、義歯、インプラント、補装具またはブレースの洗浄液および保存液である、請求項1〜9のいずれか1つに記載の方法。
- 融合タンパク質に接触する液体が、生体、特に植物および哺乳動物、好ましくはヒトに由来するかまたはそれから得られる任意の物質である、請求項1〜10のいずれか1つに記載の方法。
- 融合タンパク質に接触する液体が、医療機器、工業用水システムまたは飲料水システムの配管および天然水系の表面である、請求項1〜11のいずれか1つに記載の方法。
- 融合タンパク質と組み合わせて、またはそれに添加して抗生物質を添加することができる、請求項1〜12のいずれか1つに記載の方法。
- 細菌性バイオフィルムと関連するグラム陰性菌および/またはグラム陽性菌感染症の治療薬として使用するための、膜破壊活性またはLPS破壊活性を有するペプチドが融合されたエンドリシン、オートリシンまたはバクテリオシンを含むエンドリシンバリアント、オートリシンバリアントまたはバクテリオシンバリアント。
- 抗生物質と組み合わせて、またはそれに添加してエンドリシンバリアント、オートリシンバリアントまたはバクテリオシンバリアントが用いられる、請求項14記載の使用のためのエンドリシンバリアント、オートリシンバリアントまたはバクテリオシンバリアント。
- 食品、食品加工装置、食品加工工場、食品と接触する面、医療機器、病院または手術室における表面の細菌性バイオフィルムと関連するグラム陰性菌および/またはグラム陽性菌汚染の除去、低減および/または予防のための、膜破壊活性またはLPS破壊活性を有するペプチドが融合されたエンドリシン、オートリシンまたはバクテリオシンを含むエンドリシンバリアント、オートリシンバリアントまたはバクテリオシンバリアントの使用。
- 細菌性バイオフィルムと関連する医薬、食品もしくは飼料の診断法または環境診断法における診断手段、消毒薬または化粧用物質としての、膜破壊活性またはLPS破壊活性を有するペプチドが融合されたエンドリシン、オートリシンまたはバクテリオシンを含むエンドリシンバリアント、オートリシンバリアントまたはバクテリオシンバリアントの使用。
- エンドリシンバリアント、オートリシンバリアントまたはバクテリオシンバリアントが、抗生物質と組み合わせて、またはそれに添加して用いられる、請求項16および17に記載の使用。
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014519815A (ja) * | 2011-05-04 | 2014-08-21 | マイクレオス ヒューマン ヘルス ビー.ブイ. | ポリペプチド |
JP2016537979A (ja) * | 2013-11-14 | 2016-12-08 | ライサンド アクツィエンゲゼルシャフト | 改変されたkz144エンドリシン配列 |
JP2020504602A (ja) * | 2016-12-16 | 2020-02-13 | ウニベルシダージ ド ミーニョUniversidade Do Minho | 新規エンドリシン |
US11958890B2 (en) | 2018-05-30 | 2024-04-16 | Lysando Ag | Antimicrobial proteins |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0815484D0 (en) | 2008-08-26 | 2008-10-01 | Univ Leuven Kath | Antibacterial agents |
MX2011013288A (es) | 2009-06-26 | 2012-02-28 | Univ Leuven Kath | Agentes antimicrobianos. |
EP2446028B1 (en) | 2009-06-26 | 2018-04-04 | Lysando Aktiengesellschaft | Antimicrobial agents |
EP2470648B1 (en) * | 2009-08-24 | 2019-04-10 | Katholieke Universiteit Leuven, K.U. Leuven R&D | New endolysin obpgplys |
WO2011134998A1 (en) * | 2010-04-27 | 2011-11-03 | Lysando Holding Ag | Method of reducing biofilms |
EP2468856A1 (en) * | 2010-12-23 | 2012-06-27 | Lysando Aktiengesellschaft | Antimicrobial Agents |
JP6224069B2 (ja) * | 2012-03-23 | 2017-11-01 | アミクローブ,インコーポレイテッド | 組織適合特性を有する抗菌剤の組成物および使用 |
IN2014MN02438A (ja) | 2012-05-09 | 2015-07-10 | Contrafect Corp | |
EP2679677A1 (en) * | 2012-06-29 | 2014-01-01 | Lysando Aktiengesellschaft | Composition for use in Mycobacteria therapy |
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WO2023089544A1 (en) * | 2021-11-18 | 2023-05-25 | Sasinapas Co., Ltd. | Pharmaceutical composition comprising an endolysin or an artilysin and an anti-cancer agent |
KR102551061B1 (ko) * | 2022-05-26 | 2023-07-03 | 중앙대학교 산학협력단 | Saha를 유효성분으로 포함하는 살모넬라 속 균주에 의한 바이오필름 생성 저해용 조성물 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020037260A1 (en) * | 1997-10-16 | 2002-03-28 | Budny John A. | Compositions for treating biofilm |
WO2009041830A2 (en) * | 2007-09-25 | 2009-04-02 | Pastoral Greenhouse Gas Research Ltd | Cell-permeabilising peptides and polypeptides for microbial cells |
JP2010502735A (ja) * | 2006-09-06 | 2010-01-28 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 選択的に標的化された抗菌性ペプチドおよびその使用 |
WO2010023207A2 (en) * | 2008-08-26 | 2010-03-04 | Katholieke Universiteit Leuven K.U. Leuven R&D | Antimicrobial agents |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8816693D0 (en) | 1988-07-13 | 1988-08-17 | Agricultural & Food Res | Viral enzyme & gene |
GB0905451D0 (en) | 2009-03-31 | 2009-05-13 | Novabiotics Ltd | Biofilms |
MX2011013288A (es) * | 2009-06-26 | 2012-02-28 | Univ Leuven Kath | Agentes antimicrobianos. |
WO2011134998A1 (en) * | 2010-04-27 | 2011-11-03 | Lysando Holding Ag | Method of reducing biofilms |
-
2011
- 2011-04-27 WO PCT/EP2011/056657 patent/WO2011134998A1/en active Application Filing
- 2011-04-27 CA CA2794603A patent/CA2794603C/en active Active
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- 2011-04-27 DK DK11718001.8T patent/DK2563916T3/en active
- 2011-04-27 SG SG2012075933A patent/SG184836A1/en unknown
- 2011-04-27 EA EA201270774A patent/EA037276B1/ru not_active IP Right Cessation
- 2011-04-27 KR KR1020127031100A patent/KR20130100062A/ko not_active Application Discontinuation
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- 2011-04-27 CN CN201180032048.5A patent/CN103119158B/zh active Active
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- 2011-04-27 EP EP11718001.8A patent/EP2563916B1/en active Active
- 2011-04-27 TW TW100114595A patent/TWI527521B/zh active
-
2012
- 2012-10-25 IL IL222713A patent/IL222713A/en active IP Right Grant
-
2013
- 2013-08-15 HK HK13109541.0A patent/HK1183687A1/xx unknown
-
2016
- 2016-07-19 JP JP2016141499A patent/JP2016208985A/ja active Pending
- 2016-12-20 US US15/384,564 patent/US10485854B2/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020037260A1 (en) * | 1997-10-16 | 2002-03-28 | Budny John A. | Compositions for treating biofilm |
JP2010502735A (ja) * | 2006-09-06 | 2010-01-28 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 選択的に標的化された抗菌性ペプチドおよびその使用 |
WO2009041830A2 (en) * | 2007-09-25 | 2009-04-02 | Pastoral Greenhouse Gas Research Ltd | Cell-permeabilising peptides and polypeptides for microbial cells |
WO2010023207A2 (en) * | 2008-08-26 | 2010-03-04 | Katholieke Universiteit Leuven K.U. Leuven R&D | Antimicrobial agents |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014519815A (ja) * | 2011-05-04 | 2014-08-21 | マイクレオス ヒューマン ヘルス ビー.ブイ. | ポリペプチド |
JP2016537979A (ja) * | 2013-11-14 | 2016-12-08 | ライサンド アクツィエンゲゼルシャフト | 改変されたkz144エンドリシン配列 |
JP2020504602A (ja) * | 2016-12-16 | 2020-02-13 | ウニベルシダージ ド ミーニョUniversidade Do Minho | 新規エンドリシン |
JP7033596B2 (ja) | 2016-12-16 | 2022-03-10 | ウニベルシダージ ド ミーニョ | 新規エンドリシン |
US11958890B2 (en) | 2018-05-30 | 2024-04-16 | Lysando Ag | Antimicrobial proteins |
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MX2012012345A (es) | 2013-05-20 |
US9534223B2 (en) | 2017-01-03 |
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CA2794603A1 (en) | 2011-11-03 |
TW201204262A (en) | 2012-02-01 |
BR112012026880A2 (pt) | 2015-09-22 |
WO2011134998A8 (en) | 2011-12-15 |
US20130052182A1 (en) | 2013-02-28 |
BR112012026880B1 (pt) | 2021-03-16 |
SG184836A1 (en) | 2012-11-29 |
JP2016208985A (ja) | 2016-12-15 |
CN103119158A (zh) | 2013-05-22 |
WO2011134998A1 (en) | 2011-11-03 |
US10485854B2 (en) | 2019-11-26 |
IL222713A (en) | 2017-08-31 |
EP2563916A1 (en) | 2013-03-06 |
EA201270774A1 (ru) | 2013-04-30 |
CN103119158B (zh) | 2015-04-08 |
US20170173121A1 (en) | 2017-06-22 |
IL222713A0 (en) | 2012-12-31 |
KR20130100062A (ko) | 2013-09-09 |
EA037276B1 (ru) | 2021-03-03 |
AU2011247584A1 (en) | 2012-10-11 |
CA2794603C (en) | 2019-05-21 |
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