-
公开(公告)号：US09545431B1
公开(公告)日：2017-01-17
申请号：US12470321
申请日：2009-05-21
申请人： David M. Donovan
发明人： David M. Donovan
IPC分类号： A61K38/00
摘要： The routine use of antibiotics to battle Streptococcal pathogens has produced a new class of superbug—multi-drug resistant streptococci resulting in a need for new antimicrobials. The LambdaSa2 prophage endolysin gene harbors an amidase-5 (endopeptidase), an amidase-4 (glycosidase) domain and two Cpl-7 cell wall-binding domains. This endolysin can digest the cell walls of Streptococcus agalactiae, Streptococcus pneumoniae and Staphylococcus aureus. Turbidity reduction and plate lysis assays indicate that this peptidoglycan hydrolase also shows strong lytic activity toward Streptococcus pyogenes, Streptococcus dysgalactiae, Streptococcus uberis, Streptococcus equi, GES, and GGS. Deletion analysis on the His-tagged version of this gene further indicates that the N-terminal endopeptidase domain is minimally active in the absence of a Cpl-7 domain when lysing cells from without; however, with both Cpl-7 domains, it achieves a higher specific activity than the full length protein (on some strains) and shows weak activity against two Coagulase Negative Staphylococci, Staphylococcus hyicus and Staphylococcus xyloses.
摘要翻译： 抗生素常规使用抗链球菌病原体产生了一种新型的超耐多药耐药性链球菌，从而需要新的抗菌药物。 LambdaSa2前体细胞内溶素基因含有酰胺酶-5（内肽酶），酰胺酶-4（糖苷酶）结构域和两个Cpl-7细胞壁结合结构域。 这种内溶素可以消化无乳链球菌，肺炎链球菌和金黄色葡萄球菌的细胞壁。 浊度降低和板裂解测定表明，这种肽聚糖水解酶对于化脓性链球菌，无乳链球菌，乳房链球菌，马氏链球菌，GES和GGS也显示出强烈的溶解活性。 对该基因的His-标签版本的缺失分析进一步表明，当从没有细胞裂解细胞时，N末端内肽酶结构域在没有Cp1-7结构域的情况下是最不活跃的; 然而，对于两个Cpl-7结构域，它实现了比全长蛋白质（在一些菌株上）更高的比活性，并且对两种凝血酶阴性葡萄球菌，耻骨葡萄球菌和葡萄球菌木糖显示出弱活性。
-
2.发明申请Staphylococcus haemolyticus Prophage PhiSH2 Endolysin is Lytic for Staphylococcus aureus 有权溶血葡萄球菌菌PhiSH2内溶素是金黄色葡萄球菌的裂液公开(公告)号：US20140065127A1
公开(公告)日：2014-03-06
申请号：US13605200
申请日：2012-09-06
IPC分类号： C12N9/24
CPC分类号： C12N9/2402 , C12N9/2462 , C12Y302/01017
摘要： Methicillin-resistant (MRSA) and multi-drug resistant strains of Staphylococcus aureus are becoming increasingly prevalent in both human and veterinary clinics. S. aureus-causing bovine mastitis yields high annual losses to the dairy industry. Treatment of mastitis by broad range antibiotics is often not successful and may contribute to development of antibiotic resistance. Bacteriophage endolysins are a promising new source of antimicrobials. The endolysin of prophage φSH2 of Staphylococcus haemolyticus strain JCSC1435 (φSH2 lysin) shows lytic activity against live staphylococcal cells. Deletion constructs were tested in zymograms and turbidity reduction assays to evaluate the contribution of each functional module to lysis. The CHAP domain exhibited three-fold higher activity than the full length protein. Activity was further enhanced in the presence of bivalent calcium ions. The full length enzyme and the CHAP domain showed activity against multiple staphylococcal strains, including MRSA strains, mastitis isolates, and coagulase negative staphylococcal (CoNS) strains.
摘要翻译： 甲氧西林耐药（MRSA）和金黄色葡萄球菌多药耐药菌株在人类和兽医诊所中越来越普遍。 金黄色葡萄球菌引起的牛乳腺炎对乳制品行业的年度损失高。 通过广泛的抗生素治疗乳腺炎通常不成功，可能有助于抗生素耐药性的发展。 噬菌体内溶素是抗菌药物的有前途的新来源。 溶血葡萄球菌菌株JCSC1435（phiSH2溶素）的前噬菌体phiSH2的细胞内溶素显示对活葡萄球菌细胞的裂解活性。 在酶谱和浊度降低测定中测试缺失构建体，以评估每个功能模块对裂解的贡献。 CHAP结构域表现出比全长蛋白高三倍的活性。 在二价钙离子存在下，活性进一步提高。 全长酶和CHAP结构域显示了对多种葡萄球菌菌株的活性，包括MRSA菌株，乳腺炎分离株和凝固酶阴性葡萄球菌（CoNS）菌株。
-
3.发明授权Specific lysis of staphylococcal pathogens by bacteriophage phi11 endolysin 失效通过噬菌体phi11细胞内溶素特异性溶解葡萄球菌病原体公开(公告)号：US08361772B2
公开(公告)日：2013-01-29
申请号：US13192150
申请日：2011-07-27
申请人： David M. Donovan
发明人： David M. Donovan
摘要： The Staphylococcus aureus bacteriophage phi11 endolysin has two peptidoglycan hydrolase domains (endopeptidase and amidase) and a SH3b cell wall-binding domain. In turbidity reduction assays, the purified protein can lyse untreated staphylococcal mastitis-causing pathogens, S. aureus and coagulase negative staphylococci (S. chronogenes, S. epidermis, S. hyicus, S. simulans, S. warneri, and S. xylocus), making it a strong antimicrobial protein and an effective candidate for treating multidrug-resistant staphylococci. Lytic activity is maintained at the pH (6.7) and the ‘free’ calcium concentration (3 mM) of milk. Truncated endolysin-derived proteins, containing just the endopeptidase domain, also lyse staphylococci, in the absence of the SH3b-binding domain.
摘要翻译： 金黄色葡萄球菌噬菌体phi11细胞内溶素具有两个肽聚糖水解酶结构域（内肽酶和酰胺酶）和SH3b细胞壁结合域。 在浊度降低测定中，纯化的蛋白质可以裂解未经治疗的葡萄球菌性乳腺炎致病菌，金黄色葡萄球菌和凝固酶阴性葡萄球菌（S.chronogenes，S.表皮，猪链球菌，拟南芥，S. warneri和S.xylocus） ，使其成为强力抗菌蛋白，是治疗多重耐药性葡萄球菌的有效候选药物。 乳液活性维持在牛奶的pH（6.7）和游离钙浓度（3mM）。 在不存在SH3b结合结构域的情况下，仅含有内肽酶结构域的截短的内溶素衍生蛋白质也溶解葡萄球菌。
-
4.发明申请Specific Lysis of Staphylococcal Pathogens by Bacteriophage phi11 Endolysin 失效通过细菌噬菌体phi11特异性溶解葡萄球菌病原体公开(公告)号：US20110318328A1
公开(公告)日：2011-12-29
申请号：US13192150
申请日：2011-07-27
申请人： David M. Donovan
发明人： David M. Donovan
摘要： The Staphylococcus aureus bacteriophage phi11 endolysin has two peptidoglycan hydrolase domains (endopeptidase and amidase) and a SH3b cell wall-binding domain. In turbidity reduction assays, the purified protein can lyse untreated staphylococcal mastitis-causing pathogens, S. aureus and coagulase negative staphylococci (S. chronogenes, S. epidermis, S. hyicus, S. simulans, S. warneri, and S. xylocus), making it a strong antimicrobial protein and an effective candidate for treating multidrug-resistant staphylococci. Lytic activity is maintained at the pH (6.7) and the ‘free’ calcium concentration (3 mM) of milk. Truncated endolysin-derived proteins, containing just the endopeptidase domain, also lyse staphylococci, in the absence of the SH3b-binding domain.
摘要翻译： 金黄色葡萄球菌噬菌体phi11细胞内溶素具有两个肽聚糖水解酶结构域（内肽酶和酰胺酶）和SH3b细胞壁结合域。 在浊度降低测定中，纯化的蛋白质可以裂解未经治疗的葡萄球菌性乳腺炎致病菌，金黄色葡萄球菌和凝固酶阴性葡萄球菌（S.chronogenes，S.表皮，猪链球菌，拟南芥，S. warneri和S.xylocus） ，使其成为强力抗菌蛋白，是治疗多重耐药性葡萄球菌的有效候选药物。 乳液活性维持在pH（6.7）和牛奶的“游离”钙浓度（3mM）。 在不存在SH3b结合结构域的情况下，仅含有内肽酶结构域的截短的内溶素衍生蛋白质也溶解葡萄球菌。
-
5.发明授权公开(公告)号：US07982003B2
公开(公告)日：2011-07-19
申请号：US12498171
申请日：2009-07-06
申请人： David M. Donovan
发明人： David M. Donovan
CPC分类号： C12N9/14 , C07K2319/00 , C12N9/503 , C12N9/52 , C12N2795/00011
摘要： The invention concerns a nucleic acid encoding a recombinant bifunctional fusion peptidoglycan hydrolase protein formed from a nucleic acid encoding a peptidoglycan hydrolase module and a nucleic acid encoding a second peptidoglycan hydrolase module. The fusion, dual (or multiples thereof) peptidoglycan hydrolase modules can be used to treat disease caused by the bacteria for which the individual modules of the fusion protein are specific.
摘要翻译： 本发明涉及编码由编码肽聚糖水解酶模块的核酸和编码第二肽聚糖水解酶模块的核酸形成的重组双功能融合肽聚糖水解酶蛋白的核酸。 聚合，双重（或多个）肽聚糖水解酶模块可用于治疗由融合蛋白的各个模块特异的细菌引起的疾病。
-
6.发明授权Staphylococcus haemolyticus prophage φSH2 endolysin is lytic for Staphylococcus aureus 有权溶血葡萄球菌原噬菌体SH2细胞内溶素溶解金黄色葡萄球菌公开(公告)号：US08980614B2
公开(公告)日：2015-03-17
申请号：US13605200
申请日：2012-09-06
CPC分类号： C12N9/2402 , C12N9/2462 , C12Y302/01017
摘要： Methicillin-resistant (MRSA) and multi-drug resistant strains of Staphylococcus aureus are becoming increasingly prevalent in both human and veterinary clinics. S. aureus-causing bovine mastitis yields high annual losses to the dairy industry. Treatment of mastitis by broad range antibiotics is often not successful and may contribute to development of antibiotic resistance. Bacteriophage endolysins are a promising new source of antimicrobials. The endolysin of prophage φSH2 of Staphylococcus haemolyticus strain JCSC1435 (φSH2 lysin) shows lytic activity against live staphylococcal cells. Deletion constructs were tested in zymograms and turbidity reduction assays to evaluate the contribution of each functional module to lysis. The CHAP domain exhibited three-fold higher activity than the full length protein. Activity was further enhanced in the presence of bivalent calcium ions. The full length enzyme and the CHAP domain showed activity against multiple staphylococcal strains, including MRSA strains, mastitis isolates, and coagulase negative staphylococcal (CoNS) strains.
摘要翻译： 甲氧西林耐药（MRSA）和金黄色葡萄球菌多药耐药菌株在人类和兽医诊所中越来越普遍。 金黄色葡萄球菌引起的牛乳腺炎对乳制品行业的年度损失高。 通过广泛的抗生素治疗乳腺炎通常不成功，可能有助于抗生素耐药性的发展。 噬菌体内溶素是抗菌药物的有前途的新来源。 溶血葡萄球菌菌株JCSC1435（＆phgr。SH2溶素）的原噬菌体SH2的细胞内溶素显示对活葡萄球菌细胞的裂解活性。 在酶谱和浊度降低测定中测试缺失构建体，以评估每个功能模块对裂解的贡献。 CHAP结构域表现出比全长蛋白高三倍的活性。 在二价钙离子存在下，活性进一步提高。 全长酶和CHAP结构域显示了对多种葡萄球菌菌株的活性，包括MRSA菌株，乳腺炎分离株和凝固酶阴性葡萄球菌（CoNS）菌株。
-
7.发明申请公开(公告)号：US20130259849A1
公开(公告)日：2013-10-03
申请号：US13432758
申请日：2012-03-28
申请人： David M. Donovan , Jinzhe Mao
发明人： David M. Donovan , Jinzhe Mao
CPC分类号： A61K38/48 , C07K2319/00 , C12N9/2462 , C12Y302/01017 , C12Y305/01028
摘要： Peptidoglycan hydrolases are an effective new source of antimicrobials. A chimeric fusion protein of the Ply187 endopeptidase domain and LysK SH3b cell wall binding domain is a potent agent against Staphylococcus aureus in three functional assays.
摘要翻译： 肽聚糖水解酶是抗菌药物的有效新来源。 Ply187内肽酶结构域和LysK SH3b细胞壁结合结构域的嵌合融合蛋白是三种功能测定中金黄色葡萄球菌的有效药物。
-
8.发明授权Staphylococcal Phage2638A endolysin amidase domain is lytic for Staphylococcus aureus 有权葡萄球菌噬菌体2638A内溶素酰胺酶结构域对金黄色葡萄球菌是溶解的公开(公告)号：US09206411B2
公开(公告)日：2015-12-08
申请号：US13495536
申请日：2012-06-13
申请人： David M. Donovan , Igor V. Abaev
发明人： David M. Donovan , Igor V. Abaev
CPC分类号： C12N9/80 , A61K38/00 , A61L2/16 , C07K14/005 , C12N15/52 , C12N2795/10322 , C12N2795/10332 , C12N2795/10333 , C12Y305/01028
摘要： Staphylococcus aureus is notorious for developing resistance to virtually all antibiotics to which it is exposed. Staphylococcal phage 2638A endolysin is a peptidoglycan hydrolase that is lytic for S. aureus when exposed externally, making it a new antimicrobial candidate. It shares a common protein organization with over 40 other staphylococcal peptidoglycan hydrolases: a CHAP endopeptidase domain, a mid-protein amidase 2 domain and a C-terminal SH3b cell wall binding domain. It is the first phage endolysin reported with a cryptic translational start site between the CHAP and amidase domains. Deletion analysis indicates that the amidase domain confers most of the lytic activity and requires the full SH3b domain for maximal activity. It is common for one domain to demonstrate dominant activity over another; however, the phage 2638A endolysin is the first to show high amidase domain activity dominant over the N-terminal CHAP domain, an important finding for targeting novel peptidoglycan bonds.
摘要翻译： 金黄色葡萄球菌对于暴露于几乎所有抗生素的抗性都是臭名昭着的。 葡萄球菌噬菌体2638A细胞内溶素是一种肽聚糖水解酶，当外露时会溶解金黄色葡萄球菌，使其成为新的抗菌药物。 它与40多种其他葡萄球菌肽聚糖水解酶共享一个共同的蛋白质组织：CHAP内肽酶结构域，中蛋白酰胺酶2结构域和C末端SH3b细胞壁结合结构域。 这是第一个噬菌体内溶素与CHAP和酰胺酶结构域之间隐藏的翻译起始位点。 缺失分析表明，酰胺酶结构域赋予大部分裂解活性，并需要完整的SH3b结构域进行最大活性。 一个领域通常表现出超过另一个领域的主导地位; 然而，噬菌体2638A细胞内溶素是首先显示高N-酰基端结构域活性优于N末端CHAP结构域，这是靶向新型肽聚糖键的重要发现。
-
公开(公告)号：US08962297B2
公开(公告)日：2015-02-24
申请号：US12874138
申请日：2010-09-01
申请人： Bruce S. Seal , Gregory R. Siragusa , Ibn Mustafa A. Simmons , Johnna K. Garrish , David M. Donovan
发明人： Bruce S. Seal , Gregory R. Siragusa , Ibn Mustafa A. Simmons , Johnna K. Garrish , David M. Donovan
CPC分类号： C12N9/80 , A23K20/189 , A23K50/75 , C12N2795/10321 , C12N2795/10322 , C12N2795/10332 , C12Y305/01028
摘要： The present invention relates to isolated Clostridium perfringens bacteriophage lytic enzymes from baccteriophages CP26F and CP39O, and uses in controlling Clostridium perfringens.
摘要翻译： 本发明涉及分离出的产自嗜肺梭菌CP26F和CP39O的产气荚膜梭菌噬菌体裂解酶，并用于控制产气荚膜梭菌。
-
10.发明授权公开(公告)号：US08481289B2
公开(公告)日：2013-07-09
申请号：US12460812
申请日：2009-07-24
IPC分类号： C12P21/04
摘要： Multi-drug resistant superbugs are a persistent problem in modern health care. This invention provides an antimicrobial endolysin-Lysostaphin triple fusion protein, comprising (1) an endolysin CHAP endopeptidase domain, (2) an endolysin amidase domain, and (3) a Lysostaphin glycyl-glycine endopeptidase domain. The domains are derived from two proteins that show antimicrobial synergy when used in combination. The protein has specificity and exolytic activity for the peptidoglycan cell wall of untreated, live Staphylococcus aureus from many growth phases i.e. stationary, logarithmic and biofilm growth. The recombinant triple fusion protein comprising the three functional antimicrobial domains is designed to be refractory to resistance development.
摘要翻译： 多重耐药超细颗粒是现代医疗保健中的一个长期问题。 本发明提供了一种抗菌内溶素 - 溶葡萄球菌素三重融合蛋白，其包含（1）内溶素CHAP内肽酶结构域，（2）内溶素酰胺酶结构域，和（3）溶葡萄球菌甘氨酰 - 甘氨酸内肽酶结构域。 这些结构域来自两种结合使用时显示抗微生物协同作用的蛋白质。 该蛋白质对于来自许多生长期的未处理的活的金黄色葡萄球菌的肽聚糖细胞壁具有特异性和分解活性，即固定，对数和生物膜生长。 包含三个功能性抗微生物区域的重组三重融合蛋白被设计为耐药性发展难以治疗。
-
-
-
-
-
-
-
-
-
搜索结果
22 条记录 (耗时 0.027 秒)
