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Background: Colistin has been used as the last therapeutic resort for treatment of MDR Gram-negative bacteria infections in humans. The two-component system CpxAR has been reported to contribute to the MDR of bacteria. There may be a more complex network mediated by CpxAR contributing to colistin susceptibility than previously understood.Methods: A series of AcrB or CpxR deletion mutants of a multidrug-susceptible standard strain of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) was constructed in our previous study. MICs of colistin were determined by the 2-fold serial broth microdilution method. Time-kill and survival assays were carried out with various concentrations of colistin. Growth curves and starvation survival were measured by OD600 or cfu count in LB and M9-glucose (0.2%) minimum media. Quantitative RT-PCR was used to determine the mRNA expression levels of target genes.Results: The results showed that the MIC of colistin for the CpxR-overexpressed strain JSΔacrBΔcpxR::kan/pcpxR was dramatically decreased (0.05 mg/L) by 16-fold compared with JS (0.8 mg/L) and JSΔacrBΔcpxR::kan (0.8 mg/L). Colistin time-kill and survival assays showed that JSΔacrBΔcpxR::kan/pcpxR was more susceptible to colistin (0.05 mg/L), but had a considerably higher survivability regarding prolonged starvation stress compared with JSΔacrBΔcpxR::kan. Furthermore, the expression levels of colistin resistance-related genes (phoP, phoQ, pmrB, pmrC, pmrH and pmrD) were found to be remarkably down-regulated and the negative regulatory protein mgrB was significantly up-regulated.Conclusions: This study demonstrated that CpxR may regulate the colistin susceptibility of Salmonella Typhimurium through the PmrAB and PhoPQ regulatory systems. [ABSTRACT FROM AUTHOR]

Background: The plasmid-encoded multidrug efflux pump oqxAB confers bacterial resistance primarily to olaquindox, quinolones, and chloramphenicol. The aims of this study were to investigate the prevalence of oqxAB among Escherichia coli isolates from dogs, cats, and humans in Henan, China and the susceptibilities of E. coli isolates to common antibiotics. Methods: From 2012 to 2014, a total of 600 samples which included 400 rectal samples and 200 clinical human specimens were tested for the presence of E. coli. All isolates were screened for oqxAB genes by PCR and sequencing. The MICs of 11 antimicrobial agents were determined by the broth microdilution method. A total of 30 representative oqxAB-positive isolates were subjected to ERIC-PCR and MLST. Additionally, conjugation experiments and southern hybridizations were performed. Results: Of 270 isolates, 58.5% (62/106) of the isolates from dogs, 56.25% (36/64) of the isolates from cats, and 42.0% (42/100) of the isolates from humans were positive for the oqxAB. Olaquindox resistance was found for 85.7%-100% of oqxAB-positive isolates. Of oqxAB-positive isolates from dogs, cats, and humans, ciprofloxacin resistance was inspected for 85.8%, 59.1%, and 93.8%, respectively. Several oqxAB-positive isolates were demonstrated by ERIC-PCR and MLST, and have high similarity. Phylogenetic analysis showed that oqxAB-positive isolates could be divided into 7 major clusters. OqxAB-positive conjugants were obtained, southern hybridization verified that the oqxAB gene complex was primarily located on plasmids. Conclusion: In conclusion, oqxAB-positive isolates were widespread in animals and humans in Henan, China. Carriage of oqxAB on plasmids of E. coli isolates may facilitate the emergence of multidrug resistant and its transmission via horizontal transfer, and might pose a potential threat to public health. [ABSTRACT FROM AUTHOR]