Point Mutation Analysis of the Drug Efflux Pump MexB in Clinical Isolates of Pseudomonas aeruginosa.

Abstract

The rapid emergence of drug-resistant microbes has recently become a major concern in the medical field. In Pseudomonas aeruginosa, one of the most important mechanisms underlying antibiotic resistance is MexAB-OprM system, increases in this efflux system result in greater resistance to a wide range of drugs, and genetic mutations have been identified as a contributing factor. Thus, this study characterized point mutations in the mexB gene that are common to 39 clinical P. aeruginosa isolates obtained from The Pseudomonas Genome Database. Basic Local Alignment Search Tool (BLAST) was used to compare the mexB gene sequences of those 39 strains with PAO1. The majority of these point mutations were silent mutations without amino acid mutations. Mutations 2730, 495, and 2280, which were abundant in the strains examined, were characterized by greater codon usage after the mutation. A positive correlation has been reported between tRNA levels and codon usage in Escherichia coli, and the same relationship may be present in P. aeruginosa. In this study, the silent mutations observed in many strains mainly involved the substitution of C or G, which resulted in a higher codon usage and stronger binding power after than before the mutation. This change is considered advantageous for survival in the human body by increasing the translation efficiency of the MexB protein. Thus, combining the silent mutation identified in this study with information on the expression level of mexB is expected to be used as an indicator to identify multidrug-resistant P. aeruginosa.