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Infection and Immunity, May 2006, p. 2651-2658, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2651-2658.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Expression of Haemophilus ducreyi Collagen Binding Outer Membrane Protein NcaA Is Required for Virulence in Swine and Human Challenge Models of Chancroid

Robert A. Fulcher,1 Leah E. Cole,1,{dagger} Diane M. Janowicz,2 Kristen L. Toffer,1,{ddagger} Kate R. Fortney,2 Barry P. Katz,2 Paul E. Orndorff,5 Stanley M. Spinola,2,3,4 and Thomas H. Kawula1*

Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599,1 Department of Microbiology, Pathology and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606,5 Departments of Medicine,2 Microbiology and Immunology,3 Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 462024

Received 22 November 2005/ Returned for modification 2 January 2006/ Accepted 4 February 2006

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, CB #7290, University of North Carolina School of Medicine, Chapel Hill, NC 27599. Phone: (919) 966-9699. Fax: (919) 962-8103. E-mail: kawula{at}med.unc.edu.

Editor: D. L. Burns

{dagger} Present address: Department of Microbiology and Immunology, University of Maryland-Baltimore, Baltimore, MD 21201.

{ddagger} Present address: Pfizer Global Research and Development, Groton Laboratories, Groton, CT 06340.

Infection and Immunity, May 2006, p. 2651-2658, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2651-2658.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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