Increased glycan chain length distribution and decreased susceptibility to moenomycin in a vancomycin-resistant Staphylococcus aureus mutant

Increased glycan chain length distribution and decreased susceptibility to moenomycin in a vancomycin-resistant Staphylococcus aureus mutant
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DOI:
10.1128/aac.46.1.75-81.2002
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发表时间:
2002-01-01
影响因子:
4.9
通讯作者:
Sugai, M
Sugai, M
中科院分区:
医学2区
文献类型:
--
作者:
Komatsuzawa, H;Ohta, K;Sugai, M

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从耐甲氧西林的金黄色葡萄球菌中分离到一株耐万古霉素的金黄色葡萄球菌突变株COL-VR 1(MIC为16 μ g/ml)。暴露于万古霉素导致金黄色葡萄球菌COL。COL-VRI还显示对替考拉宁(8倍)、甲氧西林(2倍)、马卡霉素(8倍)和默诺霉素(16倍)的敏感性降低。马卡霉素和默诺霉素被认为直接抑制转糖基酶活性。突变体的表征揭示了一个增厚的细胞壁和抑制青霉素诱导的溶解,虽然量的五个青霉素结合蛋白(PBPs 1,2,3,4,和2 ')和配置文件的肽聚糖水解酶没有改变。通过反相高压液相色谱法对胞肽谱和聚糖链长度分布进行分析,结果显示与母体相比,肽交联略有减少,平均聚糖链长度增加。这些结果共同表明,转糖基酶活性在突变体中增强。这可能代表了S.金黄色。
A vancomycin-resistant Staphylococcus aureus mutant, COL-VR1 (MIC, 16 mug/ml), was isolated from methicillin-resistant S. aureus COL by exposure to vancomycin. COL-VRI also showed decreased susceptibility to teicoplanin (8-fold), methicillin (2-fold), macarbomycin (8-fold), and moenomycin (16-fold). Macarbomycin and moenomycin are thought to directly inhibit transglycosylase activity. Characterization of the mutant revealed a thickened cell wall and suppression of penicillin-induced lysis, although the amounts of the five penicillin-binding proteins (PBPs 1, 2, 3, 4, and 2') and the profiles of peptidoglycan hydrolases were not altered. Analysis of muropeptide profile and glycan chain length distribution by reversed-phase high-pressure liquid chromatography revealed slightly decreased peptide cross-linking and an increased average glycan chain length compared to those of the parent. These results together suggest that a transglycosylase activity was enhanced in the mutant. This may represent a novel mechanism of glycopeptide resistance in S. aureus.