ALTERATIONS IN VIBRIO-CHOLERAE MOTILITY PHENOTYPES CORRELATE WITH CHANGES IN VIRULENCE FACTOR EXPRESSION

Motility is thought to contribute to the virulence of Vibrio cholerae, but the role it plays in pathogenesis is not completely understood. T o investigate the influence of motility on virulence gene expression a nd intestinal colonization, we have isolated mutants with altered swar ming abilities in soft agar medium. Both spontaneous hyperswarmer (exh ibiting faster swarm rates) and spontaneous or transposon-induced nonm otile mutants of strain O395 were obtained. Surprisingly, me found tha t two of three classes of hyperswarmer mutants were defective in autoa gglutination, a phenotype associated with expression of toxin-coregula ted pill (TCP), an essential ToxR-regulated colonization factor of V. cholerae. In contrast, nonmotile mutants exhibited autoagglutination u nder growth conditions that normally repress this phenotype. Further c haracterization of mutant strains revealed differences in the expressi on of other virulence determinants. Class I hyperswarmer mutants were defective in production of TCP, cholera toxin, and a cell-associated h emolysin but showed increased levels of protease and fucose sensitive hemagglutinin. All nonmotile mutants examined, including those with in sertions in a sequence homologous to motB, exhibited increased express ion of TCP pilin, cholera toxin, and cell-associated hemolysin but dra matically decreased levels of fucose-sensitive hemagglutinin and HEp-2 adhesins. In general, nonmotile mutants displayed few or no defects i n intestinal colonization, while class I hypermotile mutants were high ly defective in colonization. These results suggest that the motility phenotype of V. cholerae is tightly coupled to the expression of multi ple ToxR-regulated and non-ToxR-regulated virulence determinants.