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Globins Synthesize the Second Messenger Bis-(3′-5′)-Cyclic Diguanosine Monophosphate in Bacteria
Authors:Xuehua Wan  Jennifer A Saito  James S Newhouse  Michael Y Galperin  Marie-Alda Gilles-Gonzalez
Institution:1 Department of Microbiology, University of Hawaii, 2538 McCarthy Mall, Snyder Hall 207, Honolulu, HI 96822, USA
2 Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
3 Maui High Performance Computing Center, 550 Lipoa Parkway, Kihei, Maui, HI 96753, USA
4 Department of Molecular Biosciences and Bioengineering, University of Hawaii, 1955 East-West Road, Honolulu, HI 96822, USA
5 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, MSC 3830, 8600 Rockville Pike, Bethesda, MD 20894, USA
6 Advanced Studies in Genomics, Proteomics, and Bioinformatics, University of Hawaii, 2565 McCarthy Mall, Honolulu, HI 96822, USA
Abstract:Globin-coupled sensors are heme-binding signal transducers in Bacteria and Archaea in which an N-terminal globin controls the activity of a variable C-terminal domain. Here, we report that BpeGReg, a globin-coupled diguanylate cyclase from the whooping cough pathogen Bordetella pertussis, synthesizes the second messenger bis-(3′-5′)-cyclic diguanosine monophosphate (c-di-GMP) upon oxygen binding. Expression of BpeGReg in Salmonella typhimurium enhances biofilm formation, while knockout of the BpeGReg gene of B. pertussis results in decreased biofilm formation. These results represent the first identification a signal ligand for any diguanylate cyclase and provide definitive experimental evidence that a globin-coupled sensor regulates c-di-GMP synthesis and biofilm formation. We propose that the synthesis of c-di-GMP by globin sensors is a widespread phenomenon in bacteria.
Keywords:BpeGReg  Bordetella pertussis globin-coupled regulator  c-di-GMP  bis-(3&prime  -5&prime  )-cyclic diguanosine monophosphate  DGC  diguanylate cyclase  EPS  exopolysaccharide  GCDC  globin-coupled diguanylate cyclase  LC  liquid chromatography  MS  mass spectrometry  TLC  thin-layer chromatography  PDE  phosphodiesterase  rdar  red  dry  and rough  SEM  scanning electron microscopy  AvGReg  A  vinelandii globin-coupled regulator  CvGReg  C  violaceum globin-coupled regulator  HPLC  high-performance liquid chromatography
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