Billot-Klein D, Gutmann L, Collatz E, van Heijenoort J
Laboratoire de Microbiologie Médicale, Université Paris VI, France.
Antimicrob Agents Chemother. 1992 Jul;36(7):1487-90. doi: 10.1128/AAC.36.7.1487.
Analysis by high-pressure liquid chromatography of the cytoplasmic peptidoglycan precursors of a high- and a low-level vancomycin-resistant Enterococcus spp. was performed before and after induction of resistance. This analysis showed a decrease of the D-Ala-D-Ala and UDP-MurNac-pentapeptide pools, an increase of the UDP-MurNac-tripeptide pool, and the appearance of new UDP-MurNac-containing material. These results lead us to suggest that the vancomycin-induced carboxypeptidase activity cleaves the D-Ala-D-Ala (L. Gutmann, D. Billot-Klein, S. Al-Obeid, I. Klare, S. Francoul, E. Collatz, and J. van Heijenoort, Antimicrob. Agents Chemother. 36:77-80, 1992), which in turn would prevent formation of the normal UDP-MurNac-pentapeptide and thereby of the vancomycin target. The novel UDP-MurNac-containing material is thought to correspond to peptidoglycan precursors which might be synthesized by an alternate pathway (T. D. H. Bugg, G. D. Wright, S. Dutka-Malen, M. Arthur, P. Courvalin, and C. T. Walsh, Biochemistry 30:10408-10415, 1991) and which would be unable to bind vancomycin in glycopeptide-resistant enterococci.
在诱导抗药性前后,对一株高耐万古霉素和一株低耐万古霉素的肠球菌属的细胞质肽聚糖前体进行了高压液相色谱分析。该分析显示,D-Ala-D-Ala和UDP-MurNac-五肽池减少,UDP-MurNac-三肽池增加,并且出现了新的含UDP-MurNac的物质。这些结果使我们推测,万古霉素诱导的羧肽酶活性可切割D-Ala-D-Ala(L. Gutmann、D. Billot-Klein、S. Al-Obeid、I. Klare、S. Francoul、E. Collatz和J. van Heijenoort,《抗菌剂与化疗》36:77-80,1992年),这反过来会阻止正常UDP-MurNac-五肽的形成,从而阻止万古霉素靶点的形成。含UDP-MurNac的新物质被认为对应于肽聚糖前体,这些前体可能通过一条替代途径合成(T. D. H. Bugg、G. D. Wright、S. Dutka-Malen、M. Arthur、P. Courvalin和C. T. Walsh,《生物化学》30:10408-10415,1991年),并且在耐糖肽肠球菌中无法与万古霉素结合。