Chancroid, an ulcerogenital disease caused by the fastidious gram-negative bacterium Haemophilus ducreyi, is one of the least understood sexually transmitted diseases. The incidence of this disease has increased dramatically in this country over the last five years, and the reported association between genital ulcer disease and transmission of the human immunodeficiency virus makes control and prevention of this disease a public health concern. This research project involves a comprehensive approach to the study of chancroid. 1) A newly developed, temperature-dependent rabbit model for lesion production by H. ducreyi will be used to investigate the pathogenesis of this disease. This model system will permit experimental investigation of basic issues related to the host-parasite interaction in chancroid. 2) Mutant analysis will be used to identify virulence factors of this pathogen. Both monoclonal antibody techniques and recombinant DNA methods will be used in conjunction with the newly developed animal model to elucidate the virulence mechanisms involved in the production of skin lesions by H. ducreyi. 3) The practical difficulties associated with making a specific diagnosis of chancroid will be addressed through the identification of diagnostic probes for this pathogen. Both monoclonal antibody- and nucleic acid-based probes will be investigated for their abilities to detect this pathogen in clinically relevant samples. Integration of studies on the pathogenesis of chancroid with efforts to develop diagnostic probes for H. ducreyi will enhance our efforts and abilities in both areas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI032011-04
Application #
2066913
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1992-01-01
Project End
1995-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Dodd, Dana A; Worth, Randall G; Rosen, Michael K et al. (2014) The Haemophilus ducreyi LspA1 protein inhibits phagocytosis by using a new mechanism involving activation of C-terminal Src kinase. MBio 5:e01178-14
Gangaiah, Dharanesh; Labandeira-Rey, Maria; Zhang, Xinjun et al. (2014) Haemophilus ducreyi Hfq contributes to virulence gene regulation as cells enter stationary phase. MBio 5:e01081-13
Labandeira-Rey, Maria; Dodd, Dana A; Brautigam, Chad A et al. (2013) The Haemophilus ducreyi Fis protein is involved in controlling expression of the lspB-lspA2 operon and other virulence factors. Infect Immun 81:4160-70
Labandeira-Rey, Maria; Brautigam, Chad A; Hansen, Eric J (2010) Characterization of the CpxRA regulon in Haemophilus ducreyi. Infect Immun 78:4779-91
Labandeira-Rey, Maria; Janowicz, Diane M; Blick, Robert J et al. (2009) Inactivation of the Haemophilus ducreyi luxS gene affects the virulence of this pathogen in human subjects. J Infect Dis 200:409-16
Labandeira-Rey, Maria; Mock, Jason R; Hansen, Eric J (2009) Regulation of expression of the Haemophilus ducreyi LspB and LspA2 proteins by CpxR. Infect Immun 77:3402-11