EFFECTS OF TEMPERATURE, NACL, AND METHICILLIN ON PENICILLIN-BINDING PROTEINS, GROWTH, PEPTIDOGLYCAN SYNTHESIS, AND AUTOLYSIS IN METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS
EFFECTS OF TEMPERATURE, NACL, AND METHICILLIN ON PENICILLIN-BINDING PROTEINS, GROWTH, PEPTIDOGLYCAN SYNTHESIS, AND AUTOLYSIS IN METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS
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DOI：
10.1128/aac.31.11.1727
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发表时间：
1987-11-01
影响因子：
4.9
通讯作者：
WILKINSON, BJ
中科院分区：
文献类型：
--
作者：
MADIRAJU, MVVS;BRUNNER, DP;WILKINSON, BJ
耐甲氧西林金黄色葡萄球菌菌株产生第五种青霉素结合蛋白（PBP），PBP 2 '，对β-内酰胺抗生素具有低亲和力，据信代表β-内酰胺不敏感的肽聚糖转肽酶。为了评价PBP 2'作为甲氧西林耐药性解释的充分性，比较了不同环境条件下PBP 2'的产生以及生长和肽聚糖合成对甲氧西林的反应。在异源甲氧西林抗性菌株DU 4916-K7中，在40 ℃下比在30 ℃下产生更少的PBP 2'，但是在40 ℃下在培养基中包含5%（wt/vol）NaCl促进PBP 2'产生，并且允许生物体在每ml 10微克甲氧西林存在下生长。当指数期培养物用甲氧西林挑战时，生长和肽聚糖合成在30 ℃下比在40 ℃下更具抗性。在培养基中加入NaCl使得生长和肽聚糖合成在40 ℃下更具甲氧西林抗性。因此，在这些条件下，PBP 2'的产生与甲氧西林抗性肽聚糖的合成之间存在良好的相关性。然而，在30 ℃下，NaCl增加了PBP 2'的产量，而没有显著影响甲氧西林的生长和肽聚糖合成的亲和性。用甲氧西林预生长细胞，预期其促进PBP 2'产生，似乎增加了生长和肽聚糖合成对甲氧西林的亲和性。在氯霉素抑制的培养物中发现了与上述相似的对甲氧西林的生长和肽聚糖合成敏感性的模式，其中推测在甲氧西林激发期间不会发生PBP 2'的诱导。在亚抑制甲氧西林和NaCl的组合中注意到复杂的影响。在NaCl的存在下，细胞的生长刺激其自溶活性，这是进一步增加了与subinhibitory甲氧西林除了NaCl的增长。NaCl似乎通过刺激PBP 2'产生和提供渗透支持来增强甲氧西林抗性，但通过刺激自溶活性来对抗它，该自溶活性由于在甲氧西林存在下生长的甲氧西林抗性菌株中肽聚糖的非常低的交联而加剧。
Methicillin-resistant Staphylococcus aureus strains produce a fifth penicillin-binding protein (PBP), PBP 2', with low affinity for beta-lactam antibiotics that is believed to represent a beta-lactam-insensitive peptidoglycan transpeptidase. In an effort to evaluate the adequacy of PBP 2' as an explanation of methicillin resistance, PBP 2' production and the responses of growth and peptidoglycan synthesis to methicillin under different environmental conditions have been compared. In the heterogeneous methicillin-resistant strain DU4916-K7, less PBP 2' was produced at 40 degrees C than at 30 degrees C, but inclusion of 5% (wt/vol) NaCl in the medium at 40 degrees C boosted PBP 2' production and allowed growth of the organism in the presence of 10 micrograms of methicillin per ml. When exponential-phase cultures were challenged with methicillin, growth and peptidoglycan synthesis were much more resistant at 30 degrees C than at 40 degrees C. Inclusion of NaCl in medium rendered growth and peptidoglycan synthesis more methicillin resistant at 40 degrees C. Hence, there was a good correlation between PBP 2' production and methicillin-resistant peptidoglycan synthesis under these conditions. However, PBP 2' production was increased by NaCl at 30 degrees C without markedly affecting the susceptibilities of growth and peptidoglycan synthesis to methicillin. Pregrowth of cells with methicillin, which was expected to boost PBP 2' production, seemed to increase the susceptibilities of growth and peptidoglycan synthesis to methicillin. Patterns of growth and peptidoglycan synthesis susceptibilities to methicillin which were similar to those described above were found in chloramphenicol-inhibited cultures, in which presumably no induction of PBP 2' could occur during the methicillin challenge period. Complex effects were noted in the combination of subinhibitory methicillin and NaCl. Growth of cells in the presence of NaCl stimulated their autolytic activity, which was further increased by growth with subinhibitory methicillin in addition to NaCl. It appears that NaCl enhances methicillin resistance by stimulating PBP 2' production and providing osmotic support but opposes it by stimulating autolytic activity which is exacerbated by the very low cross-linking of peptidoglycan in methicillin-resistant strains grown in the presence of methicillin.