PMID- 27799551 OWN - NLM STAT- MEDLINE DCOM- 20180427 LR - 20181113 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 113 IP - 46 DP - 2016 Nov 15 TI - Degradation of cyclic diguanosine monophosphate by a hybrid two-component protein protects Azoarcus sp. strain CIB from toluene toxicity. PG - 13174-13179 AB - Cyclic diguanosine monophosphate (c-di-GMP) is a second messenger that controls diverse functions in bacteria, including transitions from planktonic to biofilm lifestyles, virulence, motility, and cell cycle. Here we describe TolR, a hybrid two-component system (HTCS), from the beta-proteobacterium Azoarcus sp. strain CIB that degrades c-di-GMP in response to aromatic hydrocarbons, including toluene. This response protects cells from toluene toxicity during anaerobic growth. Whereas wild-type cells tolerated a sudden exposure to a toxic concentration of toluene, a tolR mutant strain or a strain overexpressing a diguanylate cyclase gene lost viability upon toluene shock. TolR comprises an N-terminal aromatic hydrocarbon-sensing Per-Arnt-Sim (PAS) domain, followed by an autokinase domain, a response regulator domain, and a C-terminal c-di-GMP phosphodiesterase (PDE) domain. Autophosphorylation of TolR in response to toluene exposure initiated an intramolecular phosphotransfer to the response regulator domain that resulted in c-di-GMP degradation. The TolR protein was engineered as a functional sensor histidine kinase (TolR(SK)) and an independent response regulator (TolR(RR)). This classic two-component system (CTCS) operated less efficiently than TolR, suggesting that TolR was evolved as a HTCS to optimize signal transduction. Our results suggest that TolR enables Azoarcus sp. CIB to adapt to toxic aromatic hydrocarbons under anaerobic conditions by modulating cellular levels of c-di-GMP. This is an additional role for c-di-GMP in bacterial physiology. FAU - Martin-Moldes, Zaira AU - Martin-Moldes Z AD - Department of Environmental Biology, Centro de Investigaciones Biologicas-CSIC, 28040 Madrid, Spain. FAU - Blazquez, Blas AU - Blazquez B AD - Department of Environmental Biology, Centro de Investigaciones Biologicas-CSIC, 28040 Madrid, Spain. FAU - Baraquet, Claudine AU - Baraquet C AD - Department of Microbiology, University of Washington, Seattle, WA 98195-7242. FAU - Harwood, Caroline S AU - Harwood CS AUID- ORCID: 0000-0003-4450-5177 AD - Department of Microbiology, University of Washington, Seattle, WA 98195-7242 ediaz@cib.csic.es csh5@uw.edu mtzamarro@cib.csic.es. FAU - Zamarro, Maria T AU - Zamarro MT AD - Department of Environmental Biology, Centro de Investigaciones Biologicas-CSIC, 28040 Madrid, Spain; ediaz@cib.csic.es csh5@uw.edu mtzamarro@cib.csic.es. FAU - Diaz, Eduardo AU - Diaz E AD - Department of Environmental Biology, Centro de Investigaciones Biologicas-CSIC, 28040 Madrid, Spain; ediaz@cib.csic.es csh5@uw.edu mtzamarro@cib.csic.es. LA - eng GR - R01 GM056665/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20161031 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Bacterial Proteins) RN - 0 (Membrane Proteins) RN - 3FPU23BG52 (Toluene) RN - 61093-23-0 (bis(3',5')-cyclic diguanylic acid) RN - H2D2X058MU (Cyclic GMP) SB - IM MH - Azoarcus/drug effects/*metabolism MH - Bacterial Proteins/genetics/*metabolism MH - Cyclic GMP/*analogs & derivatives/metabolism MH - Membrane Proteins/genetics/*metabolism MH - Toluene/*toxicity PMC - PMC5135311 OTO - NOTNLM OT - anaerobe OT - biodegradation OT - c-di-GMP OT - hydrocarbon tolerance OT - phosphotransfer COIS- The authors declare no conflict of interest. EDAT- 2016/11/02 06:00 MHDA- 2018/04/28 06:00 PMCR- 2017/05/15 CRDT- 2016/11/02 06:00 PHST- 2016/11/02 06:00 [pubmed] PHST- 2018/04/28 06:00 [medline] PHST- 2016/11/02 06:00 [entrez] PHST- 2017/05/15 00:00 [pmc-release] AID - 1615981113 [pii] AID - 201615981 [pii] AID - 10.1073/pnas.1615981113 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13174-13179. doi: 10.1073/pnas.1615981113. Epub 2016 Oct 31.