title: Single amino acid substitutions in the N-terminus of Vibrio cholerae TcpA affect colonization, autoagglutination, and serum resistance.
abstract: The toxin-coregulated pilus (TCP) of Vibrio cholerae O1 is required for successful infection of the host. TcpA, the structural subunit of TCP, belongs to the type IV family of pilins, which includes the PilE pilin of Neisseria gonorrhoeae. Recently, single amino acid changes in the N-terminus of PilE were found to abolish autoagglutination in gonococci. As type IV pilins demonstrate some similarities in function and amino acid sequence, site-directed mutagenesis and allelic exchanges were used to create corresponding mutations in TcpA. All four mutant strains demonstrated autoagglutination defects, and all were highly defective for colonization in the infant mouse model. These results support the previously proposed correlation between autoagglutination and colonization. Finally, all four mutants are serum sensitive, indicating that TcpA plays a role in serum resistance, a phenotype previously attributed to TcpC. As the mutations have similar effects in N. gonorrhoeae and V. cholerae, our results support the idea that type IV pilins have similar functions in a variety of pathogenic bacteria.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Chiang
authors.forename: R K
authors.initials: RK
authors.lastname: Taylor
authors.forename: M
authors.initials: M
authors.lastname: Koomey
authors.forename: J J
authors.initials: JJ
authors.lastname: Mekalanos
mesh_terms: D000483:Alleles; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D001770:Blood Bactericidal Activity; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial / Q000502:physiology*; D018390:Gene Targeting; D008074:Lipoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D013329:Structure-Activity Relationship; D014734:Vibrio cholerae / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence / Q000235:genetics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008074:Lipoproteins; C085807:TcpA protein, Vibrio cholerae; C077900:TcpC protein, Vibrio cholerae; D036781:Fimbriae Proteins