Genetic Ablation of Butyrate Utilization Attenuates Gastrointestinal Salmonella Disease

Denise N. Bronner, Franziska Faber, Erin E. Olsan, Mariana X. Byndloss, Nada A. Sayed, Gege Xu, Woongjae Yoo, Dajeong Kim, Sangryeol Ryu, Carlito B Lebrilla, Andreas J Baumler

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Salmonella enterica serovar (S.) Typhi is an extraintestinal pathogen that evolved from Salmonella serovars causing gastrointestinal disease. Compared with non-typhoidal Salmonella serovars, the genomes of typhoidal serovars contain various loss-of-function mutations. However, the contribution of these genetic differences to this shift in pathogen ecology remains unknown. We show that the ydiQRSTD operon, which is deleted in S. Typhi, enables S. Typhimurium to utilize microbiota-derived butyrate during gastrointestinal disease. Unexpectedly, genetic ablation of butyrate utilization reduces S. Typhimurium epithelial invasion and attenuates intestinal inflammation. Deletion of ydiD renders S. Typhimurium sensitive to butyrate-mediated repression of invasion gene expression. Combined with the gain of virulence-associated (Vi) capsular polysaccharide and loss of very-long O-antigen chains, two features characteristic of S. Typhi, genetic ablation of butyrate utilization abrogates S. Typhimurium-induced intestinal inflammation. Thus, the transition from a gastrointestinal to an extraintestinal pathogen involved discrete genetic changes, providing insights into pathogen evolution and emergence. Bronner et al. show that genes enabling Salmonella enterica serovar (S.) Typhimurium to utilize microbiota-derived butyrate are deleted in the genome of the closely related S. Typhi, thereby moderating intestinal inflammation induced by the pathogen. Thus, gene loss can aid in the transition from gastrointestinal to extraintestinal pathogen.

Original languageEnglish (US)
Pages (from-to)266-273.e4
JournalCell Host and Microbe
Volume23
Issue number2
DOIs
StatePublished - Feb 14 2018

Keywords

  • butyrate
  • gastroenteritis
  • pathogen evolution
  • typhoid fever

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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