Comparison of Salmonella enterica serovars Typhi and Typhimurium reveals typhoidal-specific responses to bile.


Johnson, R; Ravenhall, M; Pickard, D; Dougan, G; Byrne, A; Frankel, G; (2017) Comparison of Salmonella enterica serovars Typhi and Typhimurium reveals typhoidal-specific responses to bile. Infection and immunity. ISSN 0019-9567 DOI: https://doi.org/10.1128/IAI.00490-17

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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. RNA-Seq of S Typhi Ty2 and a clinical S Typhi isolate belonging to the globally dominant H58 lineage (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-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), 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 whilst 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 regards to virulence gene expression, which could impact pathogenesis and transmission.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Antimicrobial Resistance Centre (AMR)
PubMed ID: 29229736
URI: http://researchonline.lshtm.ac.uk/id/eprint/4645904

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