Haemophilus ducreyi, the etiologic agent of chancroid, is a major cause of genital ulcers worldwide and is increasing in prevalence in the United States. Infection with H. ducreyi appears to increase the transmission of the human immunodeficiency virus in populations where both diseases are endemic. There is no information identifying the surface components of the organism that allow it to invade epithelial surfaces and cause ulcers. The long term goal of this project is to examine the hypothesis that the major outer membrane protein (OMP) play a role in the pathogenesis of infections due to H. ducreyi. The immediate goal is to examine whether the major OMP has potential as an immune target and to examine several strains for conserved epitopes on this protein. To begin to elucidate the structure and function of the major OMP, the specific aims of this application include: 1) purification and analysis of the major OMP from a recent H. ducreyi isolate; 2) development of immunologic reagents specific for the major OMP; 3) cloning and sequencing the gene encoding the major OMP; 4) localization of epitopes on the major OMP; 5) characterization of the human immune response to the major OMP; 6) evaluation of a mouse model of H. ducreyi infection and examining whether antibodies directed against the major OMP prevent infection in this model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI027863-06
Application #
2064160
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1990-01-01
Project End
1995-06-30
Budget Start
1994-01-01
Budget End
1995-06-30
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
van Rensburg, Julia J; Lin, Huaiying; Gao, Xiang et al. (2015) The Human Skin Microbiome Associates with the Outcome of and Is Influenced by Bacterial Infection. MBio 6:e01315-15
Gangaiah, Dharanesh; Webb, Kristen M; Humphreys, Tricia L et al. (2015) Haemophilus ducreyi Cutaneous Ulcer Strains Are Nearly Identical to Class I Genital Ulcer Strains. PLoS Negl Trop Dis 9:e0003918
Holley, Concerta L; Zhang, Xinjun; Fortney, Kate R et al. (2015) DksA and (p)ppGpp have unique and overlapping contributions to Haemophilus ducreyi pathogenesis in humans. Infect Immun 83:3281-92
Holley, Concerta; Gangaiah, Dharanesh; Li, Wei et al. (2014) A (p)ppGpp-null mutant of Haemophilus ducreyi is partially attenuated in humans due to multiple conflicting phenotypes. Infect Immun 82:3492-502
Gangaiah, Dharanesh; Zhang, Xinjun; Baker, Beth et al. (2014) Haemophilus ducreyi RpoE and CpxRA appear to play distinct yet complementary roles in regulation of envelope-related functions. J Bacteriol 196:4012-25
Zhang, Xinjun; Gangaiah, Dharanesh; Munson Jr, Robert S et al. (2014) Correcting imbalanced reads coverage in bacterial transcriptome sequencing with extreme deep coverage. Int J Comput Biol Drug Des 7:195-213
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
Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R et al. (2013) Carbon storage regulator A contributes to the virulence of Haemophilus ducreyi in humans by multiple mechanisms. Infect Immun 81:608-17
Gangaiah, Dharanesh; Zhang, Xinjun; Fortney, Kate R et al. (2013) Activation of CpxRA in Haemophilus ducreyi primarily inhibits the expression of its targets, including major virulence determinants. J Bacteriol 195:3486-502
Labandeira-Rey, Maria; Dodd, Dana; Fortney, Kate R et al. (2011) A Haemophilus ducreyi CpxR deletion mutant is virulent in human volunteers. J Infect Dis 203:1859-65

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