title: MarA and ramA regulate virulence in Salmonella enterica serovar Choleraesuis.
abstract: Salmonella enterica serovar Choleraesuis is considered as an important porcine pathogen that causes serious systemic infections and exhibits poor response to treatment because of an increase in multidrug resistance (MDR). Among the various regulators of resistance, multiple antibiotic resistance factor A (marA) and regulator of acetate metabolism A (ramA) are the most effective in conferring antibiotic tolerance by activation of multidrug efflux pumps. Here we investigated the regulation of virulence in Salmonella Choleraesuis through these two transcriptional regulators. We showed that marA andramA are important for the survival of Salmonella Choleraesuis in an environment of acid and bile salts, since marA- or ramA-deficient Salmonella Choleraesuis strains failed to increase protective responses, as observed by quantitative RT-PCR (qPCR). Further, reduced invasion and survival in host cells was observed in the marA and ramA mutant strains. The results from in vitrostudies with marA- and ramA-deficient strains showed attenuated characteristics in comparison to those in the wild-type strain of Salmonella Choleraesuis when it was used to challenge BALB/c mice. The mutant strains had higher LD50 and presented poor clearance efficiency compared to the parental strain. These findings indicate that MarA and RamA not only regulate drug resistance but also play a role in the virulence of SalmonellaCholeraesuis.
authors.affiliation: Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taiwan, ROC.
authors.forename: Jen-Jie
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taiwan, ROC.
authors.forename: Shih-Ling
authors.initials: SL
authors.lastname: Hsuan
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taiwan, ROC.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taiwan, ROC.
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taiwan, ROC. Electronic address: thc@dragon.nchu.edu.tw.
authors.forename: Ter-Hsin
authors.initials: TH
authors.lastname: Chen
mesh_terms: D000143:Acids / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000737:chemistry; D002460:Cell Line; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D019779:Salmonella enterica / Q000235:genetics / Q000472:pathogenicity*; D065288:Serogroup; D013552:Swine; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000143:Acids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001647:Bile Acids and Salts; C485380:MarA protein, Salmonella enterica; C579436:RamA protein, Salmonella enterica; D015534:Trans-Activators; D037521:Virulence Factors
keywords: MarA; RamA; SalmonellaCholeraesuis; Virulence