It is well recognized that genital Chlamydia trachomatis serovars D-K are responsible for epidemic sexually transmitted diseases (STDs) in the USA, with an estimated annual 4 million cases. Chlamydial diseases can be insidious and they constitute significant primary, secondary and tertiary health care concerns in which women bear a special burden because of their increased risk of adverse reproductive consequences. Clearly, safe, effective, female-controlled topical microbicides are urgently need to help prevent and control STDs. Our previous studies showed that in human epithelial cells already infected with C, trachomatis serovar E, the microbicide C31G gains access to the chlamydial inclusions causing destruction to chlamydiae; in addition, the alteration in inclusion membrane integrity results in increased exocytosis of chlamydial LPS but not heat shock protein 60. Thus, in Specific Aim 1, we have devised a co-culture model system to determine if there is modulation of inflammatory response cell migration (PMN) to chlamydiae-infected HeLa cells exposed to C31G. My colleagues at Hershey Medical School have shown that alkyl sulfates are quite effective in killing papillomavirus, in addition to herpes simplex (HSV) and HIV. So, in Specific Aim 2, we will evaluate the action of the new topical microbicide candidate alone and in combination with C31G and alkyl sulfates on HeLa cells doubly infected with C. trachomatis and HSV. Finally, we shall use a pig model of chlamydial infection to determine or how microbicide intervention of chlamydial infection is altered in the different hormonal states (proliferative and secretory).

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI037829-08
Application #
6650580
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2002-09-01
Project End
2003-07-31
Budget Start
Budget End
Support Year
8
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Passic, Shendra R; Ferguson, Mary Lee; Catalone, Bradley J et al. (2010) Structure-activity relationships of polybiguanides with activity against human immunodeficiency virus type 1. Biomed Pharmacother 64:723-32
Pavlovic, Jelena; Floros, Joanna; Phelps, David S et al. (2008) Differentiation of xenografted human fetal lung parenchyma. Early Hum Dev 84:181-93
Beer, Brigitte E; Doncel, Gustavo F; Krebs, Fred C et al. (2006) In vitro preclinical testing of nonoxynol-9 as potential anti-human immunodeficiency virus microbicide: a retrospective analysis of results from five laboratories. Antimicrob Agents Chemother 50:713-23
Fang, L; Meyers, C; Budgeon, L R et al. (2006) Induction of productive human papillomavirus type 11 life cycle in epithelial cells grown in organotypic raft cultures. Virology 347:28-35
Hartmann, Sandra Urdaneta; Wigdahl, Brian; Neely, Elizabeth B et al. (2006) Biochemical analysis of human milk treated with sodium dodecyl sulfate, an alkyl sulfate microbicide that inactivates human immunodeficiency virus type 1. J Hum Lact 22:61-74
Deka, Srilekha; Vanover, Jennifer; Dessus-Babus, Sophie et al. (2006) Chlamydia trachomatis enters a viable but non-cultivable (persistent) state within herpes simplex virus type 2 (HSV-2) co-infected host cells. Cell Microbiol 8:149-62
Hartmann, Sandra Urdaneta; Berlin, Cheston M; Howett, Mary K (2006) Alternative modified infant-feeding practices to prevent postnatal transmission of human immunodeficiency virus type 1 through breast milk: past, present, and future. J Hum Lact 22:75-88; quiz 89-93
Fang, L; Budgeon, L R; Doorbar, J et al. (2006) The human papillomavirus type 11 E1/E4 protein is not essential for viral genome amplification. Virology 351:271-9
Urdaneta, Sandra; Wigdahl, Brian; Neely, Elizabeth B et al. (2005) Inactivation of HIV-1 in breast milk by treatment with the alkyl sulfate microbicide sodium dodecyl sulfate (SDS). Retrovirology 2:28
Krebs, Fred C; Miller, Shendra R; Ferguson, Mary Lee et al. (2005) Polybiguanides, particularly polyethylene hexamethylene biguanide, have activity against human immunodeficiency virus type 1. Biomed Pharmacother 59:438-45

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