Overexpression of an outer membrane protein associated with decreased susceptibility to carbapenems in Proteus mirabilis

PloS One
Yi-Lin TsaiShwu-Jen Liaw

Abstract

Proteus mirabilis isolates commonly have decreased susceptibility to imipenem. Previously, we found P. mirabilis hfq mutant was more resistant to imipenem and an outer membrane protein (OMP) could be involved. Therefore, we investigated the role of this OMP in carbapenem susceptibility. By SDS-PAGE we found this OMP (named ImpR) was increased in hfq mutant and LC-MS/MS revealed it to be the homologue of Salmonella YbfM, which is a porin for chitobiose and subject to MicM (a small RNA) regulation. We demonstrated that ImpR overexpression resulted in increased carbapenem MICs in the laboratory strain and clinical isolates. Chitobiose induced expression of chb (a chitobiose utilization operon). Real-time RT-PCR and SDS-PAGE were performed to elucidate the relationship of hfq, impR, chb and MicM in P. mirabilis. We found MicM RNA was decreased in hfq mutant and chbBC-intergenic region (chbBC-IGR) overexpression strain (chbIGRov), while impR mRNA was increased in hfq mutant, micM mutant and chbIGRov strain. In addition, mutation of hfq or micM and overexpression of chbBC-IGR increased ImpR protein level. Accordingly, chitobiose made wild-type have higher levels of ImpR protein and are more resistant to carbapenems. Hfq- and MicM-com...Continue Reading

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Citations

Dec 20, 2015·Future Microbiology·Joana R FelicianoJorge H Leitão
Mar 11, 2020·Frontiers in Microbiology·Delphine GirlichThierry Naas
Jul 23, 2019·Science Advances·Hanyang DongKai Zhang
Nov 25, 2020·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Marion LecuruHedi Mammeri

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Methods Mentioned

BETA
PCR
protein assay
reverse transcription PCR
Chip

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