AUTHOR=Ryan Daniel , Ojha Urmesh K. , Jaiswal Sangeeta , Padhi Chandrashekhar , Suar Mrutyunjay 

TITLE=The Small RNA DsrA Influences the Acid Tolerance Response and Virulence of Salmonella enterica Serovar Typhimurium

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.00599

DOI=10.3389/fmicb.2016.00599

ISSN=1664-302X

ABSTRACT=<p>The Gram-negative, enteropathogen <italic>Salmonella enterica</italic> serovar Typhimurium (<italic>S</italic>. Typhimurium) is exposed to various stress conditions during pathogenesis, of which acid stress serves as a major defense mechanism in the host. Such environments are encountered in the stomach and <italic>Salmonella</italic> containing vacuole of phagocytic and non-phagocytic cells. It is only recently that small RNAs (sRNAs) have come to the forefront as major regulators of stress response networks. Consequently, the sRNA DsrA which regulates acid resistance in <italic>Escherichia coli</italic>, has not been characterized in the acid tolerance response (ATR) of <italic>Salmonella.</italic> In this study, we show <italic>dsrA</italic> to be induced two and threefold under adaptation and challenge phases of the ATR, respectively. Additionally, an isogenic mutant lacking <italic>dsrA</italic> (ΔDsrA) displayed lower viability under the ATR along with reduced motility, feeble adhesion and defective invasion efficacy <italic>in vitro</italic>. Expression analysis revealed down regulation of several <italic>Salmonella</italic> pathogenicity island-1 (SPI-1) effectors in ΔDsrA compared to the wild-type, under SPI-1 inducing conditions. Additionally, our <italic>in vivo</italic> data revealed ΔDsrA to be unable to cause gut inflammation in C57BL/6 mice at 72 h post infection, although intracellular survival and systemic dissemination remained unaffected. A possible explanation may be the significantly reduced expression of flagellin structural genes <italic>fliC</italic> and <italic>fljB</italic> in ΔDsrA, which have been implicated as major proinflammatory determinants. This study serves to highlight the role of sRNAs such as DsrA in both acid tolerance and virulence of <italic>S</italic>. Typhimurium. Additionally the robust phenotype of non-invasiveness could be exploited in developing SPI-I attenuated <italic>S.</italic> Typhimurium strains without disrupting SPI-I genes.</p>