Reciprocal c-di-GMP signaling: Incomplete flagellum biogenesis triggers c-di-GMP signaling pathways that promote biofilm formation

Autoři: Daniel C. Wu aff001;  David Zamorano-Sánchez aff001;  Fernando A. Pagliai aff001;  Jin Hwan Park aff001;  Kyle A. Floyd aff001;  Calvin K. Lee aff002;  Giordan Kitts aff001;  Christopher B. Rose aff001;  Eric M. Bilotta aff002;  Gerard C. L. Wong aff002;  Fitnat H. Yildiz aff001
Působiště autorů: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, California, United States of America aff001;  Department of Bioengineering, University of California, Los Angeles, California, United States of America aff002;  Department of Chemistry and Biochemistry, University of California, Los Angeles, California, United States of America aff003;  California Nano Systems Institute, University of California, Los Angeles, California, United States of America aff004
Vyšlo v časopise: Reciprocal c-di-GMP signaling: Incomplete flagellum biogenesis triggers c-di-GMP signaling pathways that promote biofilm formation. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008703
Kategorie: Research Article


The assembly status of the V. cholerae flagellum regulates biofilm formation, suggesting that the bacterium senses a lack of movement to commit to a sessile lifestyle. Motility and biofilm formation are inversely regulated by the second messenger molecule cyclic dimeric guanosine monophosphate (c-di-GMP). Therefore, we sought to define the flagellum-associated c-di-GMP-mediated signaling pathways that regulate the transition from a motile to a sessile state. Here we report that elimination of the flagellum, via loss of the FlaA flagellin, results in a flagellum-dependent biofilm regulatory (FDBR) response, which elevates cellular c-di-GMP levels, increases biofilm gene expression, and enhances biofilm formation. The strength of the FDBR response is linked with status of the flagellar stator: it can be reversed by deletion of the T ring component MotX, and reduced by mutations altering either the Na+ binding ability of the stator or the Na+ motive force. Absence of the stator also results in reduction of mannose-sensitive hemagglutinin (MSHA) pilus levels on the cell surface, suggesting interconnectivity of signal transduction pathways involved in biofilm formation. Strains lacking flagellar rotor components similarly launched an FDBR response, however this was independent of the status of assembly of the flagellar stator. We found that the FDBR response requires at least three specific diguanylate cyclases that contribute to increased c-di-GMP levels, and propose that activation of biofilm formation during this response relies on c-di-GMP-dependent activation of positive regulators of biofilm production. Together our results dissect how flagellum assembly activates c-di-GMP signaling circuits, and how V. cholerae utilizes these signals to transition from a motile to a sessile state.

Klíčová slova:

Bacterial biofilms – Biofilms – Flagella – Flagellar motility – Gene expression – Pathogen motility – Regulator genes – Vibrio cholerae


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