PMID:16622201

Citation	Fulcher, RA, Cole, LE, Janowicz, DM, Toffer, KL, Fortney, KR, Katz, BP, Orndorff, PE, Spinola, SM and Kawula, TH (2006) Expression of Haemophilus ducreyi collagen binding outer membrane protein NcaA is required for virulence in swine and human challenge models of chancroid. Infect. Immun. 74:2651-8
Abstract	Haemophilus ducreyi, the etiologic agent of the sexually transmitted genital ulcer disease chancroid, has been shown to associate with dermal collagen fibers within infected skin lesions. Here we describe NcaA, a previously uncharacterized outer membrane protein that is important for H. ducreyi collagen binding and host colonization. An H. ducreyi strain lacking the ncaA gene was impaired in adherence to type I collagen but not fibronectin (plasma or cellular form) or heparin. The mutation had no effect on serum resistance or binding to HaCaT keratinocytes or human foreskin fibroblasts in vitro. Escherichia coli expressing H. ducreyi NcaA bound to type I collagen, demonstrating that NcaA is sufficient to confer collagen attachment. The importance of NcaA in H. ducreyi pathogenesis was assessed using both swine and human experimental models of chancroid. In the swine model, 20% of lesions from sites inoculated with the ncaA mutant were culture positive for H. ducreyi 7 days after inoculation, compared to 73% of wild-type-inoculated sites. The average number of CFU recovered from mutant-inoculated lesions was also significantly reduced compared to that recovered from wild-type-inoculated sites at both 2 and 7 days after inoculation. In the human challenge model, 8 of 30 sites inoculated with wild-type H. ducreyi progressed to the pustular stage, compared to 0 of 30 sites inoculated with the ncaA mutant. Together these results demonstrate that the collagen binding protein NcaA is required for H. ducreyi infection.
Links	PubMed PMC1459755 Online version:10.1128/IAI.74.5.2651-2658.2006
Keywords	Adhesins, Bacterial/physiology; Adult; Animals; Bacterial Adhesion; Bacterial Outer Membrane Proteins/physiology; Blood Bactericidal Activity; Chancroid/etiology; Collagen/metabolism; Disease Models, Animal; Female; Fibroblasts/microbiology; Haemophilus ducreyi/immunology; Haemophilus ducreyi/pathogenicity; Humans; Keratinocytes/microbiology; Male; Middle Aged; Swine; Virulence
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HAEDC:Q58ZK4		GO:0009279: cell outer membrane	ECO:0000314:		C		The materials and methods section entitled "Radioimmunoprecipitation of H. ducreyi outer membrane proteins" describes the process used to isolate the outer membrane proteins.	complete CACAO 5384
HAEDC:Q58ZK4		GO:0009405: pathogenesis	ECO:0000315:		P		Tables 1 and 2 show the results of inoculation of wild-type and ncaA mutant H. ducreyi. The mutant had decreased virulence in the swine (table 1) and human (table 2) models of infection compared to the wild-type.	complete CACAO 5385
HAEDC:Q58ZK4	part_of	GO:0009279: cell outer membrane	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HAEDC:Q58ZK4	involved_in	GO:0009405: pathogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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