Abstract
BackgroundThe serious human pathogen, E. coli serotype O157:H7, continues to gain antibiotic resistance, posing a public health threat. While this serotype’s genome has been sequenced, the role of 25% of its genes remains unknown, including genes conferring additional resistance. A prominent bacterial resistance mechanism is acquiring genes encoding efflux pumps, among which are the mycobacterial membrane proteins (Mmp), which contribute to virulence and membrane transport in mycobacteria. Here, we identified two potential mmp homologs (z4861 and yegN) in E. coli O157:H7, and we aimed to investigate their distribution among E. coli strains and their potential functions.Methods and resultsBy screening different E. coli strains in vitro and in silico, we observed that yegN is more conserved than z4861. Using knockout mutants lacking either or both genes, we found that the mutants were more susceptible to fluoroquinolones than the parent strain and their secretomes included fewer virulence-related proteins. Moreover, histopathological examination of the kidneys of CD-1 mice infected by the wild-type or knockout strains indicated a greater impact of z4861 on pathogenesis and kidney damage than yegN, since both mutants lacking z4861 caused less severe kidney damage. The growth pattern of the wild-type was similar to that of mutant strains under aerobic and anaerobic conditions; yet, the mutant strains grew less when treated with subinhibitory dose of ciprofloxacin.ConclusionThe previously unannotated gene product, Z4861, and its more conserved homolog, YegN, contribute to the kidney damage and resistance of E. coli O157:H7.
Highlights
The serious human pathogen, E. coli serotype O157:H7, continues to gain antibiotic resistance, posing a public health threat
We found that Z4861 and YegN contribute to the resistance of E. coli O157:H7 to fluoroquinolones
Distribution of mmpL‐like homologs among Escherichia coli strains We first investigated the frequency of distribution of z4861 and yegN genes in fully sequenced E. coli genomes and found that yegN is present more frequently than z4861
Summary
The serious human pathogen, E. coli serotype O157:H7, continues to gain antibiotic resistance, posing a public health threat. While this serotype’s genome has been sequenced, the role of 25% of its genes remains unknown, including genes conferring additional resistance. A prominent bacterial resistance mechanism is acquiring genes encoding efflux pumps, among which are the mycobacterial membrane proteins (Mmp), which contribute to virulence and membrane transport in mycobacteria. Antibiotic efflux is one of the most common resistance mechanisms in bacteria, and is promoted by efflux pumps, among which are the resistance, nodulation, and cell division (RND) transporters. A correlation between the overexpression of a prototype of RND efflux pumps and induction of spontaneous mutations within crucial genes that confer permanent antibiotic resistance has been described [11]. The driving energy for RND mediated efflux is obtained from proton motive force [13, 14]
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