Two putative MmpL homologs contribute to antimicrobial resistance and nephropathy of enterohemorrhagic O157:H7.

Background: The serious human pathogen, 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 homologs ( and ) in O157:H7, and we aimed to investigate their distribution among strains and their potential functions.

Methods And Results: By screening different strains in vitro and in silico, we observed that is more conserved than . 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 on pathogenesis and kidney damage than , since both mutants lacking 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.

Conclusion: The previously unannotated gene product, Z4861, and its more conserved homolog, YegN, contribute to the kidney damage and resistance of O157:H7.