Peschel A, Vuong C, Otto M, Götz F
Microbial Genetics, University of Tübingen, 72076 Tübingen, Germany.
Antimicrob Agents Chemother. 2000 Oct;44(10):2845-7. doi: 10.1128/AAC.44.10.2845-2847.2000.
Recently, Staphylococcus aureus strains with intermediate resistance to vancomycin, the antibiotic of last resort, have been described. Multiple changes in peptidoglycan turnover and structure contribute to the resistance phenotype. Here, we describe that structural changes of teichoic acids in the cell envelope have a considerable influence on the susceptibility to vancomycin and other glycopeptides. S. aureus cells lacking D-alanine esters in teichoic acids exhibited an at least threefold-increased sensitivity to glycopeptide antibiotics. Furthermore, the autolytic activity of the D-alanine mutant was reduced compared to the wild-type, and the mutant was more susceptible to the staphylolytic enzyme lysostaphin. Vancomycin inhibited autolysis at very high concentrations but neither in the wild-type nor in the mutant was the autolytic activity influenced in the range of the MIC. Mutant cells had a considerably higher capacity to bind vancomycin.
最近，已发现对万古霉素（最后一道防线抗生素）具有中度耐药性的金黄色葡萄球菌菌株。肽聚糖周转和结构的多种变化导致了耐药表型。在此，我们描述了细胞壁中磷壁酸的结构变化对万古霉素和其他糖肽类药物的敏感性有相当大的影响。磷壁酸中缺乏D - 丙氨酸酯的金黄色葡萄球菌细胞对糖肽类抗生素的敏感性至少提高了三倍。此外，与野生型相比，D - 丙氨酸突变体的自溶活性降低，并且该突变体对葡萄球菌溶菌酶更敏感。万古霉素在非常高的浓度下抑制自溶，但在野生型和突变体中，在MIC范围内自溶活性均未受到影响。突变体细胞结合万古霉素的能力明显更高。
