Comparison of Salmonella enterica Serovars Typhi and Typhimurium Reveals Typhoidal Serovar-Specific Responses to Bile

Abstract

Salmonella enterica serovars Typhi and Typhimurium cause typhoid fever and gastroenteritis, respectively. A unique feature of typhoid infection is asymptomatic carriage within the gallbladder, which is linked with S. Typhi transmission. Despite this, S. Typhi responses to bile have been poorly studied. Transcriptome sequencing (RNA-Seq) of S. Typhi Ty2 and a clinical S. Typhi isolate belonging to the globally dominant H58 lineage (strain 129-0238), as well as S. Typhimurium 14028, revealed that 249, 389, and 453 genes, respectively, were differentially expressed in the presence of 3% bile compared to control cultures lacking bile. fad genes, the actP-acs operon, and putative sialic acid uptake and metabolism genes (t1787 to t1790) were upregulated in all strains following bile exposure, which may represent adaptation to the small intestine environment. Genes within the Salmonella pathogenicity island 1 (SPI-1), those encoding a type IIII secretion system (T3SS), and motility genes were significantly upregulated in both S. Typhi strains in bile but downregulated in S. Typhimurium. Western blots of the SPI-1 proteins SipC, SipD, SopB, and SopE validated the gene expression data. Consistent with this, bile significantly increased S. Typhi HeLa cell invasion, while S. Typhimurium invasion was significantly repressed. Protein stability assays demonstrated that in S. Typhi the half-life of HilD, the dominant regulator of SPI-1, is three times longer in the presence of bile; this increase in stability was independent of the acetyltransferase Pat. Overall, we found that S. Typhi exhibits a specific response to bile, especially with regard to virulence gene expression, which could impact pathogenesis and transmission.

TyphoidalSalmonella: Distinctive virulence factors and pathogenesis

“…The mechanism(s) underpinning this difference are at present poorly characterized, but the stability of the dominant SPI-1 regulator HilD is increased approximately threefold in S. Typhi in bile, but decreased over threefold in S. Typhimurium in bile (Eade et al, 2016;Johnson et al, 2018). The mechanism(s) underpinning this difference are at present poorly characterized, but the stability of the dominant SPI-1 regulator HilD is increased approximately threefold in S. Typhi in bile, but decreased over threefold in S. Typhimurium in bile (Eade et al, 2016;Johnson et al, 2018).…”

“…Typhi, growth in bile results in significant upregulation of the SPI-1 T3SS and its associated genes, resulting in a significant increase in epithelial cell invasion . The mechanism(s) underpinning this difference are at present poorly characterized, but the stability of the dominant SPI-1 regulator HilD is increased approximately threefold in S. Typhi in bile, but decreased over threefold in S. Typhimurium in bile (Eade et al, 2016;Johnson et al, 2018). However, it is unknown if these changes in stability are responsible for driving changes in SPI-1 expression in bile, or rather reflects an indirect effect on HilD stability, for example, via alteration of DNA binding (as DNA-bound HilD is proposed to be more stable; Grenz, Cott Chubiz, Thaprawat, & Slauch, 2018).…”

“…Although S. Typhimurium is a commonly used and long-held model, several studies have observed marked phenotypic differences between S. Typhimurium and typhoidal serovars (Bishop et al, 2008;Elhadad et al, 2016;Elhadad, McClelland, Rahav, & Gal-Mor, 2015;Eswarappa et al, 2008;Johnson et al, 2017Johnson et al, , 2018, in addition to describing important roles for typhoidal-specific virulence factors (Haghjoo & Galán, 2004;Song, Gao, & Galán, 2013;Wilson et al, 2008Wilson et al, , 2011Winter et al, 2015;Yang et al, 2018). This review will therefore discuss what is known about virulence and pathogenesis of S. Typhi and emphasise differences between typhoidal and NTS.…”

Salmonella Extracellular Polymeric Substances Modulate Innate Phagocyte Activity and Enhance Tolerance of Biofilm-Associated Bacteria to Oxidative Stress

“…The conditions and location of these recalcitrant infections is both perplexing and problematic. Bile is rich in bile acids and bile salts with extensive immune-stimulating, antimicrobial, and detergent-like properties that can disrupt bacterial membranes, halt proton gradients, and induce redox stress [6,7]. How and why S. Typhi establishes chronic infections in such a repressive environment is not well understood [7].…”

Quantitative Assessment of an Artificial Neural Network for the Variation in Immunity to Salmonella Infection Among Sudanese and Chinese Populations and the Relationship Between HLA-DQB1 and Antibody: A Preliminary Study

“…Cases of the disease among African children decrease, and increase in the acquisition of the antibody to start all complement-dependent killing of Salmonella, and subsequently, more effective blood phagocytes and opsoniza-tion (4)(5)(6). Measuring and detecting serum antibody markers in the clinical laboratory to evaluate a patient's health status is an important and valuable issue (6)(7)(8)(9)(10)(11).…”