Inhibition of Neisseria gonorrhoeae Epithelial Cell Interactions by Vaginal Lactobacillus Species

Abstract

High levels of Lactobacillus, the dominant genus of the healthy human vaginal microbiota, have been epidemiologically linked to a reduced risk of infection following exposure to the sexually transmitted pathogen Neisseria gonorrhoeae. In this work, a cell culture model of gonococcal infection was adapted to examine the effects of lactobacilli on gonococcal interactions with endometrial epithelial cells in vitro. Precolonization of epithelial cells with Lactobacillus jensenii, Lactobacillus gasseri ATCC 33323, or L. gasseri ATCC 9857 reduced gonococcal adherence by nearly 50%. Lactobacilli also inhibited gonococcal invasion of epithelial cells by more than 60%, which was independent of the effect on adherence. Furthermore, lactobacilli were able to displace adherent gonococci from epithelial cells, suggesting that these organisms have potential as a postexposure prophylactic. Thus, vaginal lactobacilli have the ability to inhibit gonococci at two key steps of an infection, which might have a significant effect in determining whether the gonococcus will be able to successfully establish an infection following exposure in vivo.Neisseria gonorrhoeae (gonococcus), the causative agent of gonorrhea, is an obligate human pathogen that infects an estimated 62 million people per year worldwide (www.who.org). Gonorrhea is treatable with antibiotics; however, the disease is still prevalent due in part to the high frequency of asymptomatic and subclinical infections in women, providing a significant reservoir for transmission. Untreated gonococcal infections ascend the reproductive tract in up to 45% of infected women and can lead to disseminated infection, pelvic inflammatory disease, ectopic pregnancy, or sterility. Thus, gonococcal infections place a significant health burden on our society.In the initial phase of a gonococcal infection in a female host, N. gonorrhoeae adheres to receptors on epithelial cells of the genital tract. Type IV pili are the primary adhesins (28), although several additional surface structures can also mediate adherence, including lipooligosaccharide (8), porin (30), and opacity proteins (Opa and PII) (17, 31). The process of adherence is a crucial step in mounting a successful infection; if the pathogen cannot adhere, it can be swept away from the epithelial cell surface by the flow of vaginal fluid. While the flow of vaginal fluid (on average, 1.55 g/8h) is not as rapid as that of urine, if the pathogen is nonadherent, it will eventually be cleared or killed by the antimicrobial agents present in the vaginal mucus (11, 33).The indigenous microbiota plays an important role in protecting the host from colonization by incoming pathogens. Lactobacillus is the predominant genus in the vaginal (37) and endocervical microbial communities (33) and is present at concentrations of 10 7 to 10 8 CFU/ml of vaginal fluid in healthy postmenarchal/premenopausal women (22). Lactobacillus jensenii and Lactobacillus gasseri are two of the most common species present, as determined by culture-independent techniqu...

Hormone-Dependent Bacterial Growth, Persistence and Biofilm Formation – A Pilot Study Investigating Human Follicular Fluid Collected during IVF Cycles

“…This may be due to competition amongst the lactobacilli themselves, or because of alterations in adhesion. It has been reported that some bacterial species can co-colonise the surface of urogenital tract cells already colonised by lactobacilli; however, after lactobacilli are established, they can cause other species of bacterial cells to detach from the epithelium, which may offer a defence mechanism by preventing attachment of pathogens to the epithelium [29], [30]. In polymicrobial biofilms, early colonising species often promote the establishment of other species [31], [32]; however, whilst the initial interactions may be synergistic, once the biofilm is established, competition between species can result in the dominance of a single species [33].…”

The Changing Landscape of the Vaginal Microbiome

“…Thus, lactobacilli with a higher affinity for host cell receptors can displace adherent G. vaginalis and N. gonorrhoeae 25,31 . Furthermore, some lactobacilli are thought to co-aggregate with pathogens; e.g.…”

A New Era of the Vaginal Microbiome: Advances Using Next‐Generation Sequencing

“…Lactobacillus species are thought to compete for binding to receptors on host epithelial cells, and numerous studies have demonstrated that they can inhibit adherence of various urogenital pathogens including group B Streptococcus species [84], Staphylococcus aureus [84], G. vaginalis [85], N. gonorrhoeae [86], Pseudomonas aeruginosa [87], and Klebsiella pneumonia [87]. Notably, Lactobacillus species and strains vary in their ability to adhere to host cells [88] [89], which is consistent with the fact that the mechanism of competitive exclusion is only one of several defense mechanisms.…”

“…The absence of H 2 O 2 -producing lactobacilli has been associated with several unhealthy vaginal conditions and states including BV [36] [94], vaginal colonization of E. coli [95], preterm labor [96], and endometriosis [97]. Despite the consistent finding that H 2 O 2 -producing lactobacilli are associated with vaginal health, H 2 O 2 production was not found to be required for the lactic acid-induced inhibition of BV-associated bacteria [98], or with lactobacillus-induced inhibition of N. gonorrhoeae growth [89] [99]. O’Hanlon and colleagues [100] also reported that H 2 O 2 antimicrobial activities can be blocked by both semen and cervicovaginal fluid, which would suggest the mechanism may be ineffective in vivo .…”