title: The LonA Protease Regulates Biofilm Formation, Motility, Virulence, and the Type VI Secretion System in Vibrio cholerae.
abstract: The presence of the Lon protease in all three domains of life hints at its biological importance. The prokaryotic Lon protease is responsible not only for degrading abnormal proteins but also for carrying out the proteolytic regulation of specific protein targets. Posttranslational regulation by Lon is known to affect a variety of physiological traits in many bacteria, including biofilm formation, motility, and virulence. Here, we identify the regulatory roles of LonA in the human pathogen Vibrio cholerae. We determined that the absence of LonA adversely affects biofilm formation, increases swimming motility, and influences intracellular levels of cyclic diguanylate. Whole-genome expression analysis revealed that the message abundance of genes involved in biofilm formation was decreased but that the message abundances of those involved in virulence and the type VI secretion system were increased in a lonA mutant compared to the wild type. We further demonstrated that a lonA mutant displays an increase in type VI secretion system activity and is markedly defective in colonization of the infant mouse. These findings suggest that LonA plays a critical role in the environmental survival and virulence of V. cholerae.
  
  
  OBJECTIVE
  Bacteria utilize intracellular proteases to degrade damaged proteins and adapt to changing environments. The Lon protease has been shown to be important for environmental adaptation and plays a crucial role in regulating the motility, biofilm formation, and virulence of numerous plant and animal pathogens. We find that LonA of the human pathogen V. cholerae is in line with this trend, as the deletion of LonA leads to hypermotility and defects in both biofilm formation and colonization of the infant mouse. In addition, we show that LonA regulates levels of cyclic diguanylate and the type VI secretion system. Our observations add to the known regulatory repertoire of the Lon protease and the current understanding of V. cholerae physiology.
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rogers
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA.
authors.forename: Loni
authors.initials: L
authors.lastname: Townsley
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Gallego-Hernandez
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA.
authors.forename: Sinem
authors.initials: S
authors.lastname: Beyhan
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Kwuan
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA fyildiz@ucsc.edu.
authors.forename: Fitnat H
authors.initials: FH
authors.lastname: Yildiz
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D041981:Gastrointestinal Tract / Q000382:microbiology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D008124:Locomotion; D051379:Mice; D049070:Protease La / Q000235:genetics / Q000378:metabolism*; D000069376:Type VI Secretion Systems / Q000378:metabolism*; D014734:Vibrio cholerae / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D014774:Virulence
chemical_list: D000069376:Type VI Secretion Systems; D049070:Protease La