Microbiota-derived short-chain fatty acids modulate expression of Campylobacter jejuni determinants required for commensalism and virulence

Authors: LEUTHY, PAUL - University Of Texas Southwestern Medical Center; Huynh, Steven; RIBARDO, DEBORAH - University Of Texas Southwestern Medical Center; WINTER, SEBASTIAN - University Of Texas Southwestern Medical Center; Parker, Craig; HENDRIXSON, DAVID - University Of Texas Southwestern Medical Center

Submitted to: mBio
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/17/2017
Publication Date: 5/9/2017
Citation: Leuthy, P.M., Huynh, S., Ribardo, D.A., Winter, S.E., Parker, C., Hendrixson, D.R. 2017. Microbiota-derived short-chain fatty acids modulate expression of Campylobacter jejuni determinants required for commensalism and virulence. mBio. 8(3):e00407-17. doi:10.1128/mBio.00407-17.

Interpretive Summary: Campylobacter jejuni is a commensal bacteria of the intestinal tracts of avian species and other animals but a leading cause of diarrheal disease in humans. The types of cues that C. jejuni senses and responds to for promoting commensalism or infection are largely lacking. By analyzing a C. jejuni acetogenesis mutant that is defective in both converting acetyl-CoA to acetate and commensal colonization of young chicks, we discovered evidence for C. jejuni sensing spatial gradients of microbiota-derived short-chain fatty acids (SCFAs) and organic acids to modulate expression of determinants required for commensalism. We identified in C. jejuni an SCFA-influenced regulon composed by genes encoding catabolic enzymes and transport systems for amino acids that C. jejuni requires for in vivo growth. Expression of these genes was reduced in the acetogenesis mutant, but restored upon supplementation with physiological concentrations of SCFAs such as acetate and butyrate that are present in the lower intestinal tract of avian and human hosts. Conversely, the organic acid lactate, which is abundant in the upper intestinal tract of these hosts where C. jejuni less efficiently colonizes reduced expression of this regulon. We propose a model whereby C. jejuni senses microbiota-produced SCFAs and lactate for spatial orientation within the avian and human hosts. Sensing these metabolites likely allows C. jejuni to locate preferred niches in the lower intestinal tract and induce expression of factors required for in vivo growth. Our findings provide insights into the types of signals C. jejuni monitors in the avian host for commensalism and likely in the human host to promote diarrheal disease.

Technical Abstract: Campylobacter jejuni effectively promotes commensalism in the intestinal tract of avian hosts and diarrheal disease in humans, yet components of intestinal environments sensed by the bacterium in either host to initiate interactions are mostly unknown. By analyzing a C. jejuni acetogenesis mutant that is defective in both converting acetyl-CoA to acetate and commensal colonization of young chicks, we discovered evidence for C. jejuni sensing spatial gradients of microbiota-derived short-chain fatty acids (SCFAs) and organic acids to modulate expression of determinants required for commensalism. We identified in C. jejuni an SCFA-influenced regulon composed by genes encoding catabolic enzymes and transport systems for amino acids C. jejuni requires for in vivo growth. Expression of these genes was reduced in the acetogenesis mutant, but restored upon supplementation with physiological concentrations of SCFAs such as acetate and butyrate that are present in the lower intestinal tract of avian and human hosts. Conversely, the organic acid lactate, which is abundant in the upper intestinal tract of these hosts where C. jejuni less efficiently colonizes reduced expression of this regulon. We propose a model whereby C. jejuni senses microbiota-produced SCFAs and lactate for spatial orientation in the avian and human host. Sensing these metabolites likely allows C. jejuni to locate preferred niches in the lower intestinal tract and induce expression of factors required for in vivo growth. Our findings provide insights into the types of signals C. jejuni monitors in the avian host for commensalism and likely in the human host to promote diarrheal disease.