TY - JOUR
T1 - Campylobacter jejuni BumSR directs a response to butyrate via sensor phosphatase activity to impact transcription and colonization
AU - Goodman, Kyle N.
AU - Powers, Matthew J.
AU - Crofts, Alexander A.
AU - Trent, M. Stephen
AU - Hendrixson, David R.
N1 - Funding Information:
ACKNOWLEDGMENTS. This work was supported by Public Health NIH grants R01AI065539 (D.R.H.), R01HD095830 (D.R.H.), R01AI129940 (M.S.T.), R01AI138576 (M.S.T.), and R01AI150098 (M.S.T.). K.N.G. was supported by NIH training grant T32 AI007520. M.J.P. was supported by NSF Graduate Research Fellowship 049347-05. We thank Dr. Deborah Ribardo for assistance with chick colonization and qRT-PCR analyses.
Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.
PY - 2020/5/26
Y1 - 2020/5/26
N2 - 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.
AB - 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.
KW - BumS
KW - Butyrate
KW - Campylobacter jejuni
KW - Short-chain fatty acids
KW - Twocomponent signal transduction system
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U2 - 10.1073/pnas.1922719117
DO - 10.1073/pnas.1922719117
M3 - Article
C2 - 32398371
AN - SCOPUS:85085495586
SN - 0027-8424
VL - 117
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
M1 - 11715
ER -