Overexpression of an outer membrane protein associated with decreased susceptibility to carbapenems in Proteus mirabilis. 2015

Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.

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-complemented strains restored wild-type MICs. Mutation of both impR and hfq eliminated the increase in carbapenem MICs observed in hfq mutant and ImpR-complementation of hfq/impR double mutant resulted in MICs as hfq mutant, indicating that the ImpR-dependent decreased carbapenem susceptibility of hfq mutant. These indicate MicM was antisense to impR mRNA and was negatively-regulated by chbBC-IGR. Together, overexpression of ImpR contributed to the decreased carbapenem susceptibility in P. mirabilis.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D011513 Proteus mirabilis A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that is frequently isolated from clinical specimens. Its most common site of infection is the urinary tract.
D002874 Chromosome Mapping Any method used for determining the location of and relative distances between genes on a chromosome. Gene Mapping,Linkage Mapping,Genome Mapping,Chromosome Mappings,Gene Mappings,Genome Mappings,Linkage Mappings,Mapping, Chromosome,Mapping, Gene,Mapping, Genome,Mapping, Linkage,Mappings, Chromosome,Mappings, Gene,Mappings, Genome,Mappings, Linkage
D005798 Genes, Bacterial The functional hereditary units of BACTERIA. Bacterial Gene,Bacterial Genes,Gene, Bacterial
D001425 Bacterial Outer Membrane Proteins Proteins isolated from the outer membrane of Gram-negative bacteria. OMP Proteins,Outer Membrane Proteins, Bacterial,Outer Membrane Lipoproteins, Bacterial
D015780 Carbapenems A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. THIENAMYCINS are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. Antibiotics, Carbapenem,Carbapenem,Carbapenem Antibiotics
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions
D018440 beta-Lactam Resistance Nonsusceptibility of bacteria to the action of the beta-lactam antibiotics. Mechanisms responsible for beta-lactam resistance may be degradation of antibiotics by BETA-LACTAMASES, failure of antibiotics to penetrate, or low-affinity binding of antibiotics to targets. beta-Lactam Resistant,beta-Lactamase Resistance,beta-Lactamase Resistant,Resistance, beta-Lactamase,Resistant, beta-Lactamase,beta Lactam Resistance,beta Lactam Resistant,beta Lactamase Resistance,beta Lactamase Resistant

Related Publications

Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
January 1981, Archives of microbiology,
Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
June 1979, European journal of biochemistry,
Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
November 1993, Infection and immunity,
Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
March 2008, Antimicrobial agents and chemotherapy,
Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
October 1991, Infection and immunity,
Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
June 2006, International journal of antimicrobial agents,
Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
February 1975, Biochimica et biophysica acta,
Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
October 1992, Journal of clinical microbiology,
Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
January 2021, Scientific reports,
Yi-Lin Tsai, and Min-Cheng Wang, and Po-Ren Hsueh, and Ming-Che Liu, and Rouh-Mei Hu, and Yue-Jin Wu, and Shwu-Jen Liaw
March 1981, Infection and immunity,
Copied contents to your clipboard!