POINT MUTATIONS IN STAPHYLOCOCCUS-AUREUS PBP-2 GENE AFFECT PENICILLIN-BINDING KINETICS AND ARE ASSOCIATED WITH RESISTANCE
POINT MUTATIONS IN STAPHYLOCOCCUS-AUREUS PBP-2 GENE AFFECT PENICILLIN-BINDING KINETICS AND ARE ASSOCIATED WITH RESISTANCE
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DOI：
10.1128/aac.39.1.103
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发表时间：
1995-01-01
影响因子：
4.9
通讯作者：
CHAMBERS, HF
中科院分区：
文献类型：
--
作者：
HACKBARTH, CJ;KOCAGOZ, T;CHAMBERS, HF
在金黄色葡萄球菌中，青霉素结合蛋白 2 (PBP 2) 与非 PBP 2a 介导的甲氧西林耐药性有关。 PBP 2 基因 (bpbB) 是从甲氧西林敏感金黄色葡萄球菌菌株 (209P) 的表达文库中克隆的，并将其完整序列与菌株 BB255、BB255R 和 CDC6 的 pbpB 基因的序列进行比较。在 BB255R 和 CDC6（两种低水平甲氧西林耐药菌株）中检测到导致保守青霉素结合基序附近氨基酸取代的点突变。 BB255R 和 CDC6 中青霉素与 PBP 2 的结合发生了改变，动力学分析表明青霉素对 PBP 2 的结合发生改变是由于较低的结合亲和力和更快的结合药物释放。这些结构和生化变化可能导致菌株对β-内酰胺抗生素产生耐药性。
In Staphylococcus aureus, penicillin-binding protein 2 (PBP 2) has been implicated in non-PBP 2a-mediated methicillin resistance. The PBP 2 gene (bpbB) 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.