title: Alterations in Vibrio cholerae motility phenotypes correlate with changes in virulence factor expression.
abstract: Motility is thought to contribute to the virulence of Vibrio cholerae, but the role it plays in pathogenesis is not completely understood. To investigate the influence of motility on virulence gene expression and intestinal colonization, we have isolated mutants with altered swarming abilities in soft agar medium. Both spontaneous hyperswarmer (exhibiting faster swarm rates) and spontaneous or transposon-induced nonmotile mutants of strain 0395 were obtained. Surprisingly, we found that two of three classes of hyperswarmer mutants were defective in autoagglutination, a phenotype associated with expression of toxin-coregulated pili (TCP), an essential ToxR-regulated colonization factor of V. cholerae. In contrast, nonmotile mutants exhibited autoagglutination under growth conditions that normally repress this phenotype. Further characterization of mutant strains revealed differences in the expression of other virulence determinants. Class I hyperswarmer mutants were defective in production of TCP, cholera toxin, and a cell-associated hemolysin but showed increased levels of protease and fucose-sensitive hemagglutinin. All nonmotile mutants examined, including those with insertions in a sequence homologous to motB, exhibited increased expression of TCP pilin, cholera toxin, and cell-associated hemolysin but dramatically decreased levels of fucose-sensitive hemagglutinin and HEp-2 adhesins. In general, nonmotile mutants displayed few or no defects in intestinal colonization, while class I hypermotile mutants were highly defective in colonization. These results suggest that the motility phenotype of V. cholerae is tightly coupled to the expression of multiple ToxR-regulated and non-ToxR-regulated virulence determinants.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Gardel
authors.forename: J J
authors.initials: JJ
authors.lastname: Mekalanos
mesh_terms: D000371:Agglutination; D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D001483:Base Sequence; D002772:Cholera Toxin / Q000032:analysis; D010450:Endopeptidases / Q000096:biosynthesis; D036781:Fimbriae Proteins; D006460:Hemolysin Proteins / Q000096:biosynthesis; D006801:Humans; D008969:Molecular Sequence Data; D009068:Movement; D009154:Mutation; D010641:Phenotype; D014734:Vibrio cholerae / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001425:Bacterial Outer Membrane Proteins; D006460:Hemolysin Proteins; D036781:Fimbriae Proteins; D002772:Cholera Toxin; D010450:Endopeptidases