MECHANISM OF ACTION OF VANCOMYCIN - INHIBITION OF PEPTIDOGLYCAN SYNTHESIS IN GAFFKYA-HOMARI
MECHANISM OF ACTION OF VANCOMYCIN - INHIBITION OF PEPTIDOGLYCAN SYNTHESIS IN GAFFKYA-HOMARI
复制标题
DOI：
10.1128/aac.6.6.722
复制
发表时间：
1974-01-01
影响因子：
4.9
通讯作者：
NEUHAUS, FC
中科院分区：
文献类型：
--
作者：
HAMMES, WP;NEUHAUS, FC
万古霉素能抑制Gaffkya homari膜中以尿苷二磷酸-N-乙酰胞壁酰（UDP-Mur-NAc）-五肽为底物的肽聚糖合成，但对UDP-MurNAc-四肽或UDP-MurNAc-三肽均无抑制作用。这些结果与Perkins和Nieto描述的抗生素和肽亚基之间复合物形成的特异性研究相关。可以得出结论，万古霉素和假定的细胞壁受体之间或万古霉素和参与肽聚糖合成的酶之间的复合物的形成并不有助于这种抗生素的抑制作用。万古霉素对肽聚糖合成的作用机制明显不同于默诺霉素和杆菌肽。在这些抗生素的存在下，肽聚糖的合成被抑制与UDP-MurNAc-五肽和-四肽作为底物。此外，这些结果提供了额外的洞察磷酸-MurNAc-五肽易位酶的机制。例如，在低浓度的万古霉素下，用UDP-MurNAc-五肽观察到磷酸-MurNAc-肽从UDP-MurNAc-肽转移至十一异戊二烯基-磷酸的增强，而用β-四肽观察不到。万古霉素与十一异戊二烯基-二磷酸-MurNAc-五肽的复合，产生无效的中间体，将通过防止十一异戊二烯基-二磷酸-MurNAc-五肽与酶的再结合来增加转移速率。
Vancomycin inhibits the synthesis of peptidoglycan in membrane preparations fromGaffkya homariwith uridine diphosphate-N-acetylmuramyl (UDP-Mur-NAc)-pentapeptide as substrate, but not with either UDP-MurNAc-tetrapeptide or UDP-MurNAc-tripeptide. These results are correlated with the specificity studies described by Perkins and Nieto for complex formation between the antibiotic and the peptide subunit. It is concluded that the formation of a complex between vancomycin and a postulated cell wall acceptor or between vancomycin and the enzymes involved in peptidoglycan synthesis does not contribute to the inhibitory action of this antibiotic. The mechanism of vancomycin action on peptidoglycan synthesis is clearly different from that of moenomycin and bacitracin. In the presence of these antibiotics, peptidoglycan synthesis is inhibited with both UDP-MurNAc-pentapeptide and -tetrapeptide as substrates. In addition, these results provide additional insight into the mechanism of phospho-MurNAc-pentapeptide translocase. For example, enhancement of the transfer of phospho-MurNAc-peptide from UDP-MurNAc-peptide to undecaprenyl-phosphate at low concentrations of vancomycin is observed with UDP-MurNAc-pentapeptide and not with -tetrapeptide. Complexation of vancomycin with undecaprenyl-diphosphate-MurNAc-pentapeptide, resulting in an ineffective intermediate, would increase the rate of transfer by preventing the reassociation of undecaprenyl-diphosphate-MurNAc-pentapeptide with the enzyme.