金黄色葡萄球菌青霉素结合蛋白2（PBP 2）基因中的点突变影响青霉素结合动力学并与耐药性相关。
Point mutations in Staphylococcus aureus PBP 2 gene affect penicillin-binding kinetics and are associated with resistance.
作者信息
Hackbarth C J, Kocagoz T, Kocagoz S, Chambers H F
机构信息
Division of Infectious Diseases, San Francisco General Hospital, California 94110.
出版信息
Antimicrob Agents Chemother. 1995 Jan;39(1):103-6. doi: 10.1128/AAC.39.1.103.
Abstract
In Staphylococcus aureus, penicillin-binding protein 2 (PBP 2) has been implicated in non-PBP 2a-mediated methicillin resistance. The PBP 2 gene (pbpB) was cloned from an expression library of a methicillin-susceptible strain of S. aureus (209P), and its entire sequence was compared with that of the pbpB gene from strains BB255, BB255R, and CDC6. Point mutations that resulted in amino acid substitutions near the conserved penicillin-binding motifs were detected in BB255R and CDC6, two low-level methicillin-resistant strains. Penicillin binding to PBP 2 in both BB255R and CDC6 is altered, and kinetic analysis indicated that altered binding of PBP 2 by penicillin was due to both lower binding affinity and more rapid release of bound drug. These structural and biochemical changes may contribute to the strains' resistance to beta-lactam antibiotics.
摘要
在金黄色葡萄球菌中，青霉素结合蛋白2（PBP 2）与非PBP 2a介导的耐甲氧西林性有关。从一株甲氧西林敏感的金黄色葡萄球菌（209P）的表达文库中克隆出PBP 2基因（pbpB），并将其全序列与菌株BB255、BB255R和CDC6的pbpB基因序列进行比较。在两株低水平耐甲氧西林菌株BB255R和CDC6中检测到导致青霉素结合保守基序附近氨基酸替换的点突变。BB255R和CDC6中青霉素与PBP 2的结合均发生改变，动力学分析表明，青霉素对PBP 2结合的改变是由于结合亲和力降低和结合药物释放更快所致。这些结构和生化变化可能导致这些菌株对β-内酰胺类抗生素产生耐药性。
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