The Pathobiology of Neisseria gonorrhoeae Lower Female Genital Tract Infection

Abstract

Infection and disease associated with Neisseria gonorrhoeae, the gonococcus, continue to be a global health problem. Asymptomatic and subclinical gonococcal infections occur at a high frequency in females; thus, the true incidence of N. gonorrhoeae infections are presumed to be severely underestimated. Inherent to this asymptomatic/subclinical diseased state is the continued prevalence of this organism within the general population, as well as the medical, economic, and social burden equated with the observed chronic, disease sequelae. As infections of the lower female genital tract (i.e., the uterine cervix) commonly result in subclinical disease, it follows that the pathobiology of cervical gonorrhea would differ from that observed for other sites of infection. In this regard, the potential responses to infection that are generated by the female reproductive tract mucosa are unique in that they are governed, in part, by cyclic fluctuations in steroid hormone levels. The lower female genital tract has the further distinction of being able to functionally discriminate between resident commensal microbiota and transient pathogens. The expression of functionally active complement receptor 3 by the lower, but not the upper, female genital tract mucosa; together with data indicating that gonococcal adherence to and invasion of primary cervical epithelial cells and tissue are predominately aided by this surface-expressed host molecule; provide one explanation for asymptomatic/subclinical gonococcal cervicitis. However, co-evolution of the gonococcus with its sole human host has endowed this organism with variable survival strategies that not only aid these bacteria in successfully evasion of immune detection and function but also enhance cervical colonization and cellular invasion. To this end, we herein summarize current knowledge pertaining to the pathobiology of gonococcal infection of the human cervix.

Characterization of an ntrX Mutant of Neisseria gonorrhoeae Reveals a Response Regulator That Controls Expression of Respiratory Enzymes in Oxidase-Positive Proteobacteria

“…However, the decreased expression of norB observed in the Ng-ntrX mutant also likely played a predominant role in the impaired ability of mutant gonococci to survive within pex cells, as previous data indicate that nitric oxide utilization plays a paramount role in promoting gonococcal survival within pex cells (64,65). The human and bacterial responses driving the cervical tissue-gonococcus dynamic are complex (65). Therefore, additional, alternative adaptive responses controlled by the NtrYX TCS may have a contributory role in promoting the intracellular survival and growth of gonococci in the pex cell model of infection.…”

“…Hence, one of the factors that may have contributed to the failure of the gonococcal ntrX mutant to survive within pex cells may be a lowered level of cytochrome cbb 3 activity. However, the decreased expression of norB observed in the Ng-ntrX mutant also likely played a predominant role in the impaired ability of mutant gonococci to survive within pex cells, as previous data indicate that nitric oxide utilization plays a paramount role in promoting gonococcal survival within pex cells (64,65). The human and bacterial responses driving the cervical tissue-gonococcus dynamic are complex (65).…”

Prevention of preterm birth by progestational agents: what are the molecular mechanisms?

“…29 Similarly, infection of epithelial cells in the vagina and cervix has been demonstrated to be a mechanism by which Gonorrhea infection occurs. 30 Human beta defensins are a component of the innate immune system and produced by epithelial cells. The observed increase in Defensin 1 with VP may serve to enhance the antimicrobial properties of the epithelial barrier, preventing a breakdown in the epithelial barrier from infectious processes.…”

Conventional Agar-Based Culture Method, and Nucleic Acid Amplification Test (NAAT) of the cppB Gene for Detection of Neisseria gonorrhea in Pregnant Women Endocervical Swab Specimens

“…Both men and women are affected. STDs constitute a hidden epidemic of enormous physical, psychological, and economic consequences (4, 5, 12). Our data revealed that gonococcal infections could occur for asymptomatic women who had not any risk factor, and its incidence is low.…”

“…Health complications resulting from gonorrhea disease occur mainly in women, and are largely assigned to the predominately asymptomatic nature of the lower genital tract infection. Untreated, subclinical infection of the cervix can lead to upper genital tract involvement and, potentially, to infertility (4, 5). Similar to Chlamydia trachomatis, 80% of women (though only 10% of men) infected with Neisseria gonorrhea are asymptomatic, and the most common and serious complications of the infection are also infertility, ectopic pregnancy, and pelvic inflammatory disease (5, 6).…”