Effect of Drug Resistance-Associated Proteins MarA, RamA, and TolC on the Pathogenicity of Salmonella enterica serovar Choleraesuis

• Main Authors: Jen-Jie Lee, 李貞潔
• Other Authors: 陳德勛
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/01982902667856284569

博士 === 國立中興大學 === 獸醫病理生物學研究所 === 105 === As an important porcine pathogen, Salmonella enterica serovar Choleraesuis causes serious systemic infections and exhibits poor respone to treatment because of an increase in multidrug resistance. Among the various factors of resistance, global transcriptional regulators marA and ramA are thought to be effective in conferring antibiotic tolerance by activation of multidrug efflux pumps, expecially AcrAB-TolC. Here we investigated the regulation of virulence in Salmonella Choleraesuis through marA, ramA, and tolC. We showed that marA and ramA are important for the survival of Salmonella Choleraesuis in the environment of acid and bile salts. Additionally, marA and ramA are also essential for cell invasion and survival in macrophages, and the attenuation characteristics was further confirmed by in vivo study when the mutant strains were used to challenge BALB/c mice. On the other hand, we examined whether the outer membrane protein TolC, which is one of the key components of multidrug efflux pumps, involved in Salmonella Choleraesuis pathogenicity. Comparison of the acid tolerance of the tolC mutant and the parental wild-type strain showed that the absence of TolC limits the ability of Salmonella to sustain life under extremely acidic conditions. Additionally, the mutant exhibited morphological changes during growth in an acidic media, as a result of inability to fight against oxidative stress caused by acid. Furthermore, we showed that increased cellular antioxidative activity provides an overlapping protection against acid killing, demonstrating the complexity of the bacterial acid stress response. Our findings reinforce the diversity characteristics of marA, ramA, and tolC, which not only regulate drug resistance but also play roles in the virulence of Salmonella Choleraesuis.