title: The Vibrio cholerae flagellar regulatory hierarchy controls expression of virulence factors.
abstract: Vibrio cholerae is a motile bacterium responsible for the disease cholera, and motility has been hypothesized to be inversely regulated with virulence. We examined the transcription profiles of V. cholerae strains containing mutations in flagellar regulatory genes (rpoN, flrA, flrC, and fliA) by utilizing whole-genome microarrays. Results revealed that flagellar transcription is organized into a four-tiered hierarchy. Additionally, genes with proven or putative roles in virulence (e.g., ctx, tcp, hemolysin, and type VI secretion genes) were upregulated in flagellar regulatory mutants, which was confirmed by quantitative reverse transcription-PCR. Flagellar regulatory mutants exhibit increased hemolysis of human erythrocytes, which was due to increased transcription of the thermolabile hemolysin (tlh). The flagellar regulatory system positively regulates transcription of a diguanylate cyclase, CdgD, which in turn regulates transcription of a novel hemagglutinin (frhA) that mediates adherence to chitin and epithelial cells and enhances biofilm formation and intestinal colonization in infant mice. Our results demonstrate that the flagellar regulatory system modulates the expression of nonflagellar genes, with induction of an adhesin that facilitates colonization within the intestine and repression of virulence factors maximally induced following colonization. These results suggest that the flagellar regulatory hierarchy facilitates correct spatiotemporal expression patterns for optimal V. cholerae colonization and disease progression.
authors.affiliation: Department of Biology, The University of Texas at San Antonio, South Texas Center for Emerging Infectious Diseases, San Antonio, Texas 78249, USA.
authors.forename: Khalid Ali
authors.initials: KA
authors.lastname: Syed
authors.forename: Sinem
authors.initials: S
authors.lastname: Beyhan
authors.forename: Nidia
authors.initials: N
authors.lastname: Correa
authors.forename: Jessica
authors.initials: J
authors.lastname: Queen
authors.forename: Jirong
authors.initials: J
authors.lastname: Liu
authors.forename: Fen
authors.initials: F
authors.lastname: Peng
authors.forename: Karla J F
authors.initials: KJ
authors.lastname: Satchell
authors.forename: Fitnat
authors.initials: F
authors.lastname: Yildiz
authors.forename: Karl E
authors.initials: KE
authors.lastname: Klose
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D001422:Bacterial Adhesion; D018441:Biofilms / Q000254:growth & development; D002460:Cell Line; D004912:Erythrocytes; D005407:Flagella / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006384:Hemagglutination; D006388:Hemagglutinins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D007422:Intestines / Q000382:microbiology; D051379:Mice; D009154:Mutation; D014158:Transcription, Genetic; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D006388:Hemagglutinins; D037521:Virulence Factors