In Vitro and in Vivo Models for Pathogenic Neisseria gonorrhoeae Infections

Introduction

Sexually transmitted diseases (STDs) are infections caused by pathogens that are transmitted from one person to another via any type of sexual contact. There are several STDs caused by different pathogens such as virus, bacteria and parasites (Lunzen and Altfeld, 2014). One of the major burdens faced by the world today is the sexually transmitted infection (STI) caused by a species of the genus Neisseria (Trevisan, 1885), Neisseria gonorrhoeae, the pathogen which causes the human disease called gonorrhea. This bacterium is known to affect an average of 60-65 million people worldwide every year (Woods, 2005).The disease caused by the bacterium, gonorrhea, is the second most reported sexually transmitted disease in the USA and, reference to its existence can be traced back as far as to “biblical times” (Lev. 15:1-15:19).The causative agent N. gonorrhoeae of the disease gonorrhea was discovered by a German physician, Albert Ludwig Sigesmund Neisser, in 1879 (Ligon, 2005). N. gonorrhoeae, a gram-negative bacterium, is an obligate human pathogen which often causes infection at the mucosal sites of the urogenital tracts causing STI. Gonorrhea can affect almost anyone who is sexually active; younger women who are less than 25 years of age, older women with many sexual partners, and homosexuals are very susceptible. Neisseria infection is both symptomatic and asymptomatic with most women depicting the latter form of the disease. The disease may manifest just a few days or weeks’ post-infection leading to several complications (Detels et al. 2011).

Gonorrhea may be posing high susceptibility to HIV (Human Immunodeficiency Virus) and Chlamydia trachomatis(which causes the STI chlamydia). It has been studied that infection by N. Gonorrhoeaemay be posing a high risk for also transmitting HIV (Monty Montano et al, 2007). N. gonorrhoea had been initially treated with penicillin and then with other antibiotics such as cephalosporins, fluoroquinolones and tetracyclines, which significantly reduced the incidence of the disease; yet the crisis of antibiotic resistance made the treatment and cure ineffectual leading to the high prevalence of the disease. This antibiotic resistance ability of the bacteria had made the CDC (Communicable Disease Center) CDC categorize them as ‘superbugs’ (Unemo et al., 2016).

The basis of gonococcal infection (i.e. from gonococcus, the pus-producing bacterium (N. gonorrhoeae) that causes gonorrhea in humans depends on the adherence of the bacterium to the epithelia and anti-adherent agents have been tried and tested as a treatment. One study showed the efficacy of the lactobacillus, a microbiota that produces lactic acid, against the adherence of gonococcus. N. gonorrhoeae bacterium is highly capable of immune evasion due to its ability to alter the antigenic determinants (Edwards and Apicella, 2004), i.e. to escape the immune response.

It has been studied that gonococcal lipo-oligosaccharide and peptidoglycan induces proinflammatory cytokines and chemokines which further initiate a cascade of events. Phagocytic cells are employed at the site, and these initiate immune responses elicited by the body. This produces reactive oxygen and nitrogen species thereby causing cytotoxic effects to the cells (Rahal et al., 2014). But, the strong antioxidant system of the bacteria comprising of catalase, superoxide dismutase, ABC type Mn transporter and cytochrome c peroxidase, enables them to defend and survive in such environments (Speers-Roesch and Ballantyne, 2005). Symptomatic infections are characterized by flooding of numerous polymorphonuclear neutrophils (PMNs), the most numerous granulocytes (white blood cell), and the gonococcus is found intracellular to it (Johnson and Criss, 2011) i.e., infected individuals contain large numbers of PMNs with ingested gonococci (Simons et al., 2005).

There is a strong requirement of appropriate data for the interpretation of the disease related studies which will enable the development of disease selective and sensitive drugs. The use of various relevant animal models, organ and cell line models for the research and developmental studies of Neisserial infections has provided significant information for the interpretation and extrapolation of the data, through the years. These models provided valuable toolsf or various molecular mechanism studies and, drug discovery and development studies.