MarA and ramA regulate virulence in Salmonella enterica serovar Choleraesuis

• Published in: Veterinary microbiology 2015-12, Vol.181 (3-4), p.323-327
• Main Authors: Lee, Jen-Jie, Hsuan, Shih-Ling, Kuo, Chih-Jung, Wu, Ying-Chen, Chen, Ter-Hsin
• Format: Article
• Language: English
• Subjects: Acids - chemistry; Animals; Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bile Acids and Salts - chemistry; Cell Line; Female; Gene Expression Regulation, Bacterial; MarA; Mice; Mice, Inbred BALB C; RamA; Salmonella enterica - genetics; Salmonella enterica - pathogenicity; SalmonellaCholeraesuis; Serogroup; Swine; Trans-Activators - genetics; Trans-Activators - metabolism; Virulence; Virulence - genetics; Virulence Factors - genetics; Virulence Factors - metabolism
• ISSN: 0378-1135; 1873-2542
• DOI: 10.1016/j.vetmic.2015.09.006

•MarA and RamA are crucial for Salmonella Choleraesuis to endure the extreme environments in gastrointestinal tracts.•MarA or RamA truncation affects the invasion or survival ability of SalmonellaCholeraesuis in host cells.•Mice present higher LD50 after administration of mutantSalmonella Choleraesuis than parental strain. 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.