Campylobacter jejuni BumSR directs a response to butyrate via sensor phosphatase activity to impact transcription and colonization

Kyle N. Goodman, Matthew J. Powers, Alexander A. Crofts, M. Stephen Trent, David R. Hendrixson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Campylobacter jejuni monitors intestinal metabolites produced by the host and microbiota to initiate intestinal colonization of avian and animal hosts for commensalism and infection of humans for diarrheal disease. We previously discovered that C. jejuni has the capacity to spatially discern different intestinal regions by sensing lactate and the short-chain fatty acids acetate and butyrate and then alter transcription of colonization factors appropriately for in vivo growth. In this study, we identified the C. jejuni butyratemodulated regulon and discovered that the BumSR two-component signal transduction system (TCS) directs a response to butyrate by identifying mutants in a genetic screen defective for butyratemodulated transcription. The BumSR TCS, which is important for infection of humans and optimal colonization of avian hosts, senses butyrate likely by indirect means to alter transcription of genes encoding important colonization determinants. Unlike many canonical TCSs, the predicted cytoplasmic sensor kinase BumS lacked in vitro autokinase activity, which would normally lead to phosphorylation of the cognate BumR response regulator. Instead, BumS has likely evolved mutations to naturally function as a phosphatase whose activity is influenced by exogenous butyrate to control the level of endogenous phosphorylation of BumR and its ability to alter transcription of target genes. To our knowledge, the BumSR TCS is the only bacterial signal transduction system identified so far that mediates responses to the microbiota-generated intestinal metabolite butyrate, an important factor for host intestinal health and homeostasis. Our findings suggest that butyrate sensing by this system is vital for C. jejuni colonization of multiple hosts.

Original languageEnglish (US)
Article number11715
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
StatePublished - May 26 2020


  • BumS
  • Butyrate
  • Campylobacter jejuni
  • Short-chain fatty acids
  • Twocomponent signal transduction system

ASJC Scopus subject areas

  • General


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