C-di-GMP Regulates Motile to Sessile Transition by Modulating MshA Pili Biogenesis and Near-Surface Motility Behavior in Vibrio cholerae.
In many bacteria, including Vibrio cholerae, cyclic dimeric guanosine monophosphate (c-di-GMP) controls the motile to biofilm life style switch. Yet, little is known about how this occurs. In this study, we report that changes in c-di-GMP concentration impact the biosynthesis of the MshA pili, resulting in altered motility and biofilm phenotypes in V. cholerae. Previously, we reported that cdgJ encodes a c-di-GMP phosphodiesterase and a ΔcdgJ mutant has reduced motility and enhanced biofilm formation. Here we show that loss of the genes required for the mannose-sensitive hemagglutinin (MshA) pilus biogenesis restores motility in the ΔcdgJ mutant. Mutations of the predicted ATPase proteins mshE or pilT, responsible for polymerizing and depolymerizing MshA pili, impair near surface motility behavior and initial surface attachment dynamics. A ΔcdgJ mutant has enhanced surface attachment, while the ΔcdgJmshA mutant phenocopies the high motility and low attachment phenotypes observed in a ΔmshA strain. Elevated concentrations of c-di-GMP enhance surface MshA pilus production. MshE, but not PilT binds c-di-GMP directly, establishing a mechanism for c-di-GMP signaling input in MshA pilus production. Collectively, our results suggest that the dynamic nature of the MshA pilus established by the assembly and disassembly of pilin subunits is essential for transition from the motile to sessile lifestyle and that c-di-GMP affects MshA pilus assembly and function through direct interactions with the MshE ATPase.
Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
Christopher J
CJ
Jones
Department of Bioengineering, Department of Chemistry and Biochemistry, California Nano Systems Institute, University of California, Los Angeles, Los Angeles, California, United States of America.
Andrew
A
Utada
Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
Kimberly R
KR
Davis
Department of Chemistry, Stanford University, Stanford, California, United States of America.
Wiriya
W
Thongsomboon
Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
David
D
Zamorano Sanchez
Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
Vinita
V
Banakar
Department of Chemistry, Stanford University, Stanford, California, United States of America.
Lynette
L
Cegelski
Department of Bioengineering, Department of Chemistry and Biochemistry, California Nano Systems Institute, University of California, Los Angeles, Los Angeles, California, United States of America.
Gerard C L
GC
Wong
Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
Fitnat H
FH
Yildiz
D018441:Biofilms; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004843:Epistasis, Genetic; D036781:Fimbriae Proteins / Q000096:biosynthesis*; D010861:Fimbriae, Bacterial / Q000187:drug effects* / Q000502:physiology; D037601:Mannose-Binding Lectin / Q000096:biosynthesis; D009068:Movement; D014734:Vibrio cholerae / Q000187:drug effects* / Q000502:physiology
D037601:Mannose-Binding Lectin; C101032:MshA protein, Vibrio cholerae; D036781:Fimbriae Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP