Mechanisms of host manipulation by Neisseria gonorrhoeae

Abstract

Neisseria gonorrhoeae (also known as gonococcus) has been causing gonorrhoea in humans since ancient Egyptian times. Today, global gonorrhoea infections are rising at an alarming rate, in concert with an increasing number of antimicrobial-resistant strains. The gonococcus has concurrently evolved several intricate mechanisms that promote pathogenesis by evading both host immunity and defeating common therapeutic interventions. Central to these adaptations is the ability of the gonococcus to manipulate various host microenvironments upon infection. For example, the gonococcus can survive within neutrophils through direct regulation of both the oxidative burst response and maturation of the phagosome; a concerning trait given the important role neutrophils have in defending against invading pathogens. Hence, a detailed understanding of how N. gonorrhoeae exploits the human host to establish and maintain infection is crucial for combating this pathogen. This review summarizes the mechanisms behind host manipulation, with a central focus on the exploitation of host epithelial cell signaling to promote colonization and invasion of the epithelial lining, the modulation of the host immune response to evade both innate and adaptive defenses, and the manipulation of host cell death pathways to both assist colonization and combat antimicrobial activities of innate immune cells. Collectively, these pathways act in concert to enable N. gonorrhoeae to colonize and invade a wide array of host tissues, both establishing and disseminating gonococcal infection.

Thyroglossal Duct Cyst Infection Caused by Neisseria gonorrhoeae: An Unusual Complication of Pharyngeal Gonorrhea

“…A variety of adhesins mediate this process including pili, lipooligosaccharide, and the outer membrane protein porin. Foremost among these determinants is the opacity-associated protein (Opa), a diverse population of molecules 19,20 that bind to select carcinoembryonic antigen cell adhesion (CEACAMs) molecules [19][20][21] located on the host cell surface. In a murine model of meningococcal infection, both CEACAM1 and Opa protein expressions were a necessary prerequisite both for nasopharyngeal colonization and for neutrophil recruitment and infiltration to the nasal mucosal.…”

“…23 Second, in vitro studies have shown that a palette of CEACAMs expressed on cell types encountered by the gonococcus serve as receptors for gonococcal Opa proteins. 24 Third, this specific Opa-CEACAM interaction in the gonococcus has been shown to govern the cell tropism 19,20,25 and host immune/inflammatory response. 19,20,25 Oropharyngeal colonization by the gonococcus has been suspected to facilitate the emergence of antibiotic-resistant gonorrhea as reflected by the diminished clinical and microbiological cure rates after antibiotic treatment [26][27][28] of infection at this site.…”

“…24 Third, this specific Opa-CEACAM interaction in the gonococcus has been shown to govern the cell tropism 19,20,25 and host immune/inflammatory response. 19,20,25 Oropharyngeal colonization by the gonococcus has been suspected to facilitate the emergence of antibiotic-resistant gonorrhea as reflected by the diminished clinical and microbiological cure rates after antibiotic treatment [26][27][28] of infection at this site. A potential explanation lies in the interspecies horizontal transfer of resistant genes after encounters by the gonococcus with nonpathogenic commensal Neisseria species that are inhabitants of the host residential microflora.…”

“…Second, in vitro studies have shown that a palette of CEACAMs expressed on cell types encountered by the gonococcus serve as receptors for gonococcal Opa proteins 24 . Third, this specific Opa-CEACAM interaction in the gonococcus has been shown to govern the cell tropism 19,20,25 and host immune/inflammatory response 19,20,25 …”

Copper management strategies in obligate bacterial symbionts: balancing cost and benefit

“…The majority of Neisseria species are obligate symbionts that predominantly colonize mucosae of mammalian hosts [ 57 ]. Among them, Neisseria meningitidis [ 58 ] and Neisseria gonorrhoeae [ 59 ] have been extensively studied due to their pathogenic potential. These bacteria primarily adopt a mucosal-associated extracellular lifestyle with limited intracellular survival capabilities [ 56 ].…”