Influence of the Anti-HIV drug Elvitegravir on Chlamydial Development and the Characterization of Chlamydial Polymorphic Membrane Protein Expression in Herpes Simplex Virus (HSV)/C. trachomatis Co-infected Cells
Date of Award
Thesis Professor Department
Laraine Powers, Frank Hagelberg
Chlamydia trachomatis is the most common bacterial agent of sexually transmitted infections worldwide and a common co-infection in AIDS patients. Chlamydial genital tract infections are often asymptomatic; therefore many infections go untreated and result in complications like chronic inflammation, ectopic pregnancy, and pelvic inflammatory disease. Chlamydia share a unique developmental cycle and under stress, can enter a state known as persistence, in which the bacteria are noninfectious but still viable. Removal of the stressor allows the chlamydiae to re-enter and complete the developmental cycle. Exposure to low-dose quinolones can cause the chlamydiae to enter persistence and halt the developmental cycle. Notably, 1 in 20 people living with HIV/AIDS also suffers from chlamydial infections. Since the anti-HIV drug Elvitegravir (EVG) is a quinolone derivative, we hypothesized that EVG exposure would inhibit chlamydial development. To ascertain whether EVG affects chlamydial development, HeLa cells were infected with C. trachomatis or C. muridarum and then either mock treated or treated with EVG. The percent infectivity and production of infectious progeny were determined by immunofluorescence assay and chlamydial titer assay, respectively. Transmission electron microscopy (TEM) was used to examine chlamydial morphology and determine whether EVG caused Chlamydia to become persistent. Though percent infectivity and chlamydial morphology were similar between treated and untreated Chlamydia-infected cells, the production of infectious progeny was significantly decreased in EVG-exposed Chlamydia-infected cells. These data indicate that EVG is not a persistence-inducer, but does inhibit chlamydial development in vitro. In other studies, we tested chlamydial polymorphic membrane protein (PMP) expression in chlamydia/HSV co-infected cells by immunofluorescence staining. Since penicillin-induced persistence decreases the expression of some chlamydial PMPs, we hypothesized that expression of PMP-A and PMP-B would be decreased by HSV-induced persistence. The results indicated that there was no significant difference in expression of PMP-A or PMP-B in co-infected versus C. trachomatis singly-infected cells. These data suggest that PMP expression is not a good indicator of chlamydial persistence when induced by HSV.
Honors Thesis - Withheld
Yakoob, Hena, "Influence of the Anti-HIV drug Elvitegravir on Chlamydial Development and the Characterization of Chlamydial Polymorphic Membrane Protein Expression in Herpes Simplex Virus (HSV)/C. trachomatis Co-infected Cells" (2015). Undergraduate Honors Theses. Paper 259. https://dc.etsu.edu/honors/259
Copyright by the authors.