c-di-GMP inhibits LonA-dependent proteolysis of TfoY in Vibrio cholerae

Autoři: Avatar Joshi aff001;  Samar A. Mahmoud aff002;  Soo-Kyoung Kim aff003;  Justyne L. Ogdahl aff002;  Vincent T. Lee aff003;  Peter Chien aff002;  Fitnat H. Yildiz aff001
Působiště autorů: Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, United States of America aff001;  Department of Biochemistry and Molecular Biology, Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, Massachusetts, United States of America aff002;  Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, United States of America aff003
Vyšlo v časopise: c-di-GMP inhibits LonA-dependent proteolysis of TfoY in Vibrio cholerae. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008897
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008897


The LonA (or Lon) protease is a central post-translational regulator in diverse bacterial species. In Vibrio cholerae, LonA regulates a broad range of behaviors including cell division, biofilm formation, flagellar motility, c-di-GMP levels, the type VI secretion system (T6SS), virulence gene expression, and host colonization. Despite LonA’s role in cellular processes critical for V. cholerae’s aquatic and infectious life cycles, relatively few LonA substrates have been identified. LonA protease substrates were therefore identified through comparison of the proteomes of wild-type and ΔlonA strains following translational inhibition. The most significantly enriched LonA-dependent protein was TfoY, a known regulator of motility and the T6SS in V. cholerae. Experiments showed that TfoY was required for LonA-mediated repression of motility and T6SS-dependent killing. In addition, TfoY was stabilized under high c-di-GMP conditions and biochemical analysis determined direct binding of c-di-GMP to LonA results in inhibition of its protease activity. The work presented here adds to the list of LonA substrates, identifies LonA as a c-di-GMP receptor, demonstrates that c-di-GMP regulates LonA activity and TfoY protein stability, and helps elucidate the mechanisms by which LonA controls important V. cholerae behaviors.

Klíčová slova:

Biofilms – Gene expression – Cholera – Pathogen motility – Proteases – Proteolysis – Regulator genes – Secretion systems


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