No abstract

Presently marketed vaginal barrier agents are cytotoxic and damage the vaginal epithelium and natural vaginal flora with frequent use. Novel noncytotoxic agents are needed to protect women from sexually transmitted diseases. One candidate compound is a high-molecular-mass form of soluble poly(sodium 4-styrene sulfonate) (T-PSS). The antimicrobial activity of T-PSS was evaluated in primary culture systems and in a genital herpes murine model. Results obtained indicate that T-PSS is highly effective against herpes simplex viruses, Neisseria gonorrhoeae, and Chlamydia trachomatis in vitro. A 5% T-PSS gel protected 15 of 16 mice from vaginal herpes, compared with 2 of 16 mice treated with a placebo gel. Moreover, T-PSS exhibited little or no cytotoxicity and has an excellent selectivity index. T-PSS is an excellent candidate topical antimicrobial that blocks adherence of herpes simplex virus at low concentrations, inactivates virus at higher concentrations, and exhibits a broad spectrum of antimicrobial activity.

We evaluated mucosal attachment, colonization, and invasion by Haemophilus influenzae in an experimental model of human nasopharyngeal tissue in organ culture. Nonpiliated, encapsulated, and nonencapsulated, IgA1 protease-deficient mutants of H. influenzae were compared with their isogenic IgA1 protease-producing parents. Damage to peripheral ciliary activity was first noted 6 hr after infection and was associated with sloughing of ciliated cells to which H. influenzae were not attached. Infection of organ cultures with each strain resulted in similar degrees and rates of ciliary damage. H. influenzae attached selectively to nonciliated epithelial cells or was associated with surface mucus. Later, disruption of epithelial tight junctions was observed, and clusters of H. influenzae were found between epithelial cells. Organisms were also seen within phagocytic vacuoles of mononuclear cells located above and below the basement membrane. In summary, encapsulated and nonencapsulated H. influenzae damaged the ciliary function of human nasopharyngeal organ cultures, attached to the mucosal surface, and invaded the epithelium. H. influenzae IgA1 protease, however, was not essential for the pathogenic steps observed in this human nasopharyngeal organ culture model.

b -galactoside. Galectin-3 had the highest affinity for the nLc 6 LOS, which is made by a strain that is highly infectious for the male urethra, but also bound nLc 4 LOS and to a Lac LOS. The lacto-N -neotetraose tetrasaccharide was a more potent inhibitor of galectin-3 binding to LOS than either lactose or N -acetyllactosamine. The relative affinity of galectin-3 for gonococci mirrored its affinity for purified LOS. Western blot analysis revealed expression of galectin-3 by human endometrial adenocarcinoma and prostatic epithelial cells that can be invaded by gonococci. Immunohistochemistry of human fallopian tube epithelium showed localized expression of galectin-3 by non-ciliated cells, the specific cell gonococci invade in this tissue. We conclude that because of its location and affinity for gonococcal LOS galectin-3 could play a role in gonococcal infection.

Heparan sulfate (HS) serves as a receptor for adherence of herpes simplex viruses, Chlamydia trachomatis, Neisseria gonorrhoeae, and, indirectly, human immunodeficiency virus. Using primary human culture systems, we identified sulfated carbohydrate compounds that resemble HS and competitively inhibit infection by these pathogens. These compounds are candidates for intravaginal formulations for the prevention of sexually transmitted diseases.