Told you it might work for VD. Here it s............................ F239: Susceptibility of Chlamydia trachomatis to Recombinant Bactericidal/Permeability Increasing Protein (rBPI-21) Lewis Lambert, Eddie Bautista, Steve Carroll and Pat Scannon. XOMA Corporation, Berkeley, CA 94710. Chlamydia trachomatis (Ct) is the leading cause of preventable blindness in the world and the most prevalent sexually transmitted disease in industrialized countries. The Ct outer membrane contains both a heparan sulfate-like glycosaminoglycan host cell surface attachment molecule and lipopolysaccharide (LPS). Previous studies have demonstrated rBPI-21 binds to both of these complex polysaccharides with high affinity. In addition, rBPI-21 exhibits antimicrobial activity to a variety of gram-negative and positive bacteria. Here, we examined the effect of rBPI-21 on both the attachment and viability of Ct using a microtiter tray modification of the shell vial assay. Chlamydia trachomatis serovar L2 was exposed to decreasing concentrations of rBPI-21 for up to 30 minutes at 37°C prior to infection of McCoy cells. The cells were washed after a 2 hr exposure to the inoculum and cultured for 48 - 72 hrs. Inclusion bodies were counted after detection using the Syva MicroTrakr Culture Confirmation procedure. rBPI-21 rapidly and completely inhibited infection and/or propagation of the treated elementary bodies (EBs) at concentrations down to 4 ug/mL. To evaluate whether rBPI-21 could affect established infections, McCoy cells were infected with EBs for 2 hrs, washed and treated with decreasing concentrations of rBPI-21 in EMEM. The cells were cultured for 48 - 72 hrs and the numbers of inclusion bodies scored as previously described. At concentrations of >/= 16 ug/mL, rBPI-21 markedly reduced but did not eliminate the inclusion bodies. These results may be due to the intracellular inhibition of the reticulate bodies (RBs) and/or prevention of secondary infection by EBs. Our data suggest that rBPI-21, a well tolerated analog of a human neutrophil protein, may be useful in treating ophthalmic and other topical infections caused by this important and pervasive pathogen. c Copyright 1996, XOMA Corporation
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