Walsh F, Amyes S G B
University of Edinburgh, United Kingdom.
J Chemother. 2007 Aug;19(4):376-81. doi: 10.1179/joc.2007.19.4.376.
The objectives of this study were to identify the carbapenem resistance mechanisms of clinical Pseudomonas aeruginosa isolates. The strains resistant to imipenem had lost only the OprD protein, the isolates resistant to imipenem and meropenem had both loss of the OprD porin and reduced minimum inhibitory concentrations (MICs) in the presence of efflux pump inhibitors. In the isolates in which efflux had been identified (n=2) only 1 isolate had a mutation in the mexR gene corresponding to a glutamine to a stop codon change at amino acid 106. This has not been previously identified. There were no significant changes in the mexT genes. No mutations previously associated with the upregulation of the carbapenem efflux pumps in in vitro generated resistant isolates were identified in any of the clinical isolates. Therefore, the resistance mechanisms identified by development of carbapenem resistance in vitro are not sufficient to understand carbapenem resistance development in clinical isolates.
本研究的目的是确定临床分离的铜绿假单胞菌对碳青霉烯类抗生素的耐药机制。对亚胺培南耐药的菌株仅失去了外膜孔蛋白D(OprD),对亚胺培南和美罗培南均耐药的菌株既失去了OprD孔蛋白,又在存在外排泵抑制剂的情况下最低抑菌浓度(MIC)降低。在已鉴定出存在外排作用的分离株(n = 2)中,只有1株在mexR基因中发生了突变,对应于第106位氨基酸由谷氨酰胺突变为终止密码子。这在以前尚未被发现。mexT基因没有显著变化。在任何临床分离株中均未鉴定出先前与体外诱导产生的耐药分离株中碳青霉烯类抗生素外排泵上调相关的突变。因此,体外产生碳青霉烯类抗生素耐药性所确定的耐药机制不足以解释临床分离株中碳青霉烯类抗生素耐药性的产生。