Gonorrhea – an evolving disease of the new millennium

Abstract

Etiology, transmission and protection: Neisseria gonorrhoeae (the gonococcus) is the etiological agent for the strictly human sexually transmitted disease gonorrhea. Infections lead to limited immunity, therefore individuals can become repeatedly infected. Pathology/symptomatology: Gonorrhea is generally a non-complicated mucosal infection with a pustular discharge. More severe sequellae include salpingitis and pelvic inflammatory disease which may lead to sterility and/or ectopic pregnancy. Occasionally, the organism can disseminate as a bloodstream infection. Epidemiology, incidence and prevalence: Gonorrhea is a global disease infecting approximately 60 million people annually. In the United States there are approximately 300, 000 cases each year, with an incidence of approximately 100 cases per 100,000 population. Treatment and curability: Gonorrhea is susceptible to an array of antibiotics. Antibiotic resistance is becoming a major problem and there are fears that the gonococcus will become the next “superbug” as the antibiotic arsenal diminishes. Currently, third generation extended-spectrum cephalosporins are being prescribed. Molecular mechanisms of infection: Gonococci elaborate numerous strategies to thwart the immune system. The organism engages in extensive phase (on/off switching) and antigenic variation of several surface antigens. The organism expresses IgA protease which cleaves mucosal antibody. The organism can become serum resistant due to its ability to sialylate lipooligosaccharide in conjunction with its ability to subvert complement activation. The gonococcus can survive within neutrophils as well as in several other lymphocytic cells. The organism manipulates the immune response such that no immune memory is generated which leads to a lack of protective immunity.

The challenge of converting Gram‐positive‐only compounds into broad‐spectrum antibiotics

“…Fastidious bacteria, such as Neisseria gonorrhoeae and Helicobacter pylori, have complex nutritional requirements, and their outer membranes are significantly different than those of nonfastidious organisms. [122][123][124] The same is true for Mycobacteria, which are often considered Gramnegative because they do not stain with Gram stain. However, unlike traditional Gram-negative species that contain an LPS layer, Mycobacteria contain a mycolic acid layer.…”

“…For this study, we focused on compounds with activity against Enterobacteriaceae ( E. coli and Klebsiella ), P. aeruginosa , and/or A. baumannii , which are all nonfastidious Gram‐negative organisms. Fastidious bacteria, such as Neisseria gonorrhoeae and Helicobacter pylori , have complex nutritional requirements, and their outer membranes are significantly different than those of nonfastidious organisms . The same is true for Mycobacteria , which are often considered Gram‐negative because they do not stain with Gram stain.…”

Photo-inactivation ofNeisseria gonorrhoeae: A paradigm changing approach for combating antibiotic-resistant gonococcal infection

“…N. gonorrhoeae have evolved the mechanism to invade into human vaginal epithelial cells to overcome host defense barrier (48). To assess the effectiveness of 405-nm aBL inactivation of intracellular N. gonorrhoeae, VK2/E6E7 cells were seeded into a 35-mm petri dish (Transwell ® , Costar, NY, USA) at a cell density of 2 × 10 5 cells/dish.…”

Secretion of Chromosomal DNA by the Neisseria gonorrhoeae Type IV Secretion System

“…In the majority of cases, gonorrhea is an uncomplicated mucosal infection, but if left untreated gonorrhea can cause severe complications like pelvic inflammatory disease, infertility, neonatal conjunctivitis, septic arthritis, blindness and disseminated gonococcal infections (Unemo 2015; Hill et al 2016). The type IV secretion system (T4SS) of Neisseria gonorrhoeae is the only known T4SS that secretes ssDNA into the extracellular milieu (Dillard and Seifert 2001; Hamilton et al 2005).…”

“…N. gonorrhoeae elaborates different surface-exposed components such as type IV pili and opacity proteins which frequently undergo phase- and antigenic variation allowing for efficient evasion of the host immune system (Hill et al 2016). Moreover, the ability to rapidly exchange DNA, mutations and a high recombination rate promote spread of resistances against various antimicrobials, which is a major health concern.…”