Genetic Ablation of Butyrate Utilization Attenuates Gastrointestinal Salmonella Disease.

Bronner DN, Faber F, Olsan EE, Byndloss MX, Sayed NA, Xu G, Yoo W, Kim D, Ryu S, Lebrilla CB, Bäumler AJ
Cell Host Microbe. 2018 23 (2): 266-273.e4

PMID: 29447698 · PMCID: PMC6345573 · DOI:10.1016/j.chom.2018.01.004

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.

Copyright © 2018 Elsevier Inc. All rights reserved.

MeSH Terms (15)

Animals Butyrates Cell Line, Tumor Clostridium Colitis Escherichia coli Female Humans Intestines Mice Mice, Inbred CBA Salmonella Food Poisoning Salmonella typhi Salmonella typhimurium Type III Secretion Systems

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