The Acid Tolerance Response of Salmonella Typhimurium: Global Transcriptome and Mutagenic Analysis

ABSTRACT

Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causative agents of food-borne bacterial gastroenteritis. Swift invasion through the intestinal tract and successful establishment in systemic organs is associated with the adaptability of S. Typhimurium to different stress environments. Low pH stress serves as one of the first lines of defense in mammalian hosts, which S. Typhimurium must efficiently overcome to establish an infection. Therefore, a better understanding of the molecular mechanisms underlying the adaptability of S. Typhimurium to acid stress is highly relevant. In this study, we have performed a transcriptome analysis of S. Typhimurium under the acid tolerance response (ATR) and found a large number of genes (∼47%) to be differentially expressed (>1.5-fold; <-1.5-fold; p<0.01). Functional annotation revealed differentially expressed genes to be associated with regulation, metabolism, transport & binding, pathogenesis and motility. Additionally, our knockout analysis of a subset of differentially regulated genes facilitated the identification of proteins that contribute to S. Typhimurium ATR and virulence. Mutants, lacking genes encoding the K⁺ binding and transport protein KdpA, hypothetical protein YciG, the flagella hook cap protein FlgD, and the nitrate reductase subunit NarZ were significantly deficient in their ATR's and displayed varied in-vitro virulence characteristics. This study offers a greater insight into the transcriptome changes of S. Typhimurium under the ATR and provides a framework for further research on the subject.