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  • Review Article
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Neisseria gonorrhoeae host adaptation and pathogenesis

Nature Reviews Microbiology volume 16, pages 226–240 (2018)Cite this article

Subjects

Key Points

  • The urogenital tract is a complex environment composed of many different types of epithelial tissues and innate immune cells that sample the surrounding milieu. As a host-adapted organism, Neisseria gonorrhoeae can interact with only human forms of many molecules. Moreover, owing to environmental heterogeneities as well as unknown concentrations of oxygen and nutrients in this niche, substantial challenges exist for developing tissue culture and animal models. Advances in standardizing the cell culture techniques of primary tissue culture and transgenic mouse models may help to ameliorate these challenges.

  • Although the prevailing view is that infections in women are mainly asymptomatic whereas infections in men are not, many studies show that asymptomatic infections are prevalent in both sexes. The observations underlying the current dogma likely come from physiological and anatomical differences in the male and female urogenital tracts, making neutrophil influx in men much more noticeable and easier to diagnose than infections in women.

  • N. gonorrhoeae is an obligate human pathogen with the ability to evade and modulate both the innate and adaptive immune systems to benefit its replication and survival. The host-restricted pathogen has subsequently evolved a moderately small but effective set of regulatory mechanisms to quickly adapt to changing oxygen and nutrient concentrations.

  • As N. gonorrhoeae progresses through the stages of disease pathogenesis (transmission, adherence, colonization and invasion, and immune evasion), the bacterium expresses many virulence factors to promote survival and replication while remaining minimally invasive and minimally discoverable by immune cells. It has yet to be settled in the field whether the vast neutrophil influx following symptomatic infection benefits the host or the pathogen.

  • Owing to its natural competence, propensity for horizontal gene transfer, efficient transformation and dynamic and variable genome, N. gonorrhoeae is rapidly developing resistance to every major class of antibiotic. With worldwide antimicrobial resistance on the rise, it is necessary to understand the mechanisms by which resistance determinants confer resistance and to develop novel therapies to avoid an era of untreatable gonorrhoea.

  • The Neisseria genus is composed of many commensals and one other pathogen, Neisseria meningitidis, that are closely related to N. gonorrhoeae genetically but are phenotypically distinct and occupy different niches. Owing to this similarity, it is often difficult to determine which factors are specific virulence factors for N. gonorrhoeae and which facilitate colonization. More research is needed to determine which factors confer pathogenicity and differentiate between these two pathogens.

Abstract

The host-adapted human pathogen Neisseria gonorrhoeae is the causative agent of gonorrhoea. Consistent with its proposed evolution from an ancestral commensal bacterium, N. gonorrhoeae has retained features that are common in commensals, but it has also developed unique features that are crucial to its pathogenesis. The continued worldwide incidence of gonorrhoeal infection, coupled with the rising resistance to antimicrobials and the difficulties in controlling the disease in developing countries, highlights the need to better understand the molecular basis of N. gonorrhoeae infection. This knowledge will facilitate disease prevention, surveillance and control, improve diagnostics and may help to facilitate the development of effective vaccines or new therapeutics. In this Review, we discuss sex-related symptomatic gonorrhoeal disease and provide an overview of the bacterial factors that are important for the different stages of pathogenesis, including transmission, colonization and immune evasion, and we discuss the problem of antibiotic resistance.

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Figure 1: Overview of Neisseria gonorrhoeae infection.
Figure 2: Overview of Neisseria gonorrhoeae pathogenesis factors.
Figure 3: Overview of transcriptional regulatory factors of Neisseria gonorrhoeae.
Figure 4: Neisseria gonorrhoeae evades and modulates the innate and adaptive immune systems.
Figure 5: Antibiotic resistance in Neisseria gonorrhoeae.

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Acknowledgements

H.S.S. was supported by the US National Institutes of Health (NIH) grant R37-AI033493. S.J.Q. was partially supported by NIH grant T32-AI0007476.

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  1. Department of Microbiology–Immunology, Northwestern University Feinberg School of Medicine, Chicago, 60611, Illinois, USA

    Sarah Jane Quillin & H Steven Seifert

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  1. Sarah Jane Quillin
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S.J.Q. and H.S.S. contributed to researching data for the article. S.J.Q. and H.S.S. substantially contributed to the discussion of content. S.J.Q. and H.S.S. wrote the article. S.J.Q. and H.S.S. reviewed and edited the manuscript before submission.

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Glossary

Exotoxins

Bacterial secreted proteins that damage host cells.

Pelvic inflammatory disease

A clinical syndrome where infected fallopian tube tissues are damaged by the host inflammatory response to bacteria.

Ectopic pregnancy

A sequela of pelvic inflammatory disease that occurs when a fertilized egg implants anywhere other than the uterine lining, such as in the fallopian tube, which risks organ damage and blood loss.

Purulent exudate

The hallmark symptom of gonorrhoea; a liquid genital secretion composed of neutrophils and Neisseria gonorrhoeae.

Microcolonies

Collections of bacterial cells that exist as discrete formations.

Antigenic variation

A reversible process by which a microorganism provides many different versions of a gene product at a frequency higher than the normal mutation rate.

Phase variation

A stochastic form of genetic change that varies gene expression on/off or up/down.

Biofilms

Structured formations of bacterial cells within an extracellular matrix that stick to one another and together on a surface.

C4b-binding protein

(C4BP). A classical complement pathway regulatory protein, akin to factor H in the alternative pathway, that regulates complement activation on host cells.

Factor H

A control protein of the alternative complement pathway that binds C3b, displacing activated factor Bb and enabling cleavage and subsequent inactivation of C3b by factor I-induced conversion to iC3b.

Oxidative burst

An antimicrobial response through the release of reactive oxygen species from host cells.

Transcytosis

The transit of the cellular epithelium by a bacterium.

Nutritional immunity

The ability of the host to sequester important nutrients during infection.

Siderophores

Low molecular mass iron-binding chemical compounds secreted by bacteria to chelate iron for subsequent uptake into the bacterial cell.

Microaerophilic

Environments where oxygen concentration is limited but not zero.

Alternative complement pathway

One arm of the complement system that is triggered by C3b binding to a microorganism or other surface, damaged tissue and foreign material.

Classical complement pathway

One arm of the complement system triggered by antigen–antibody complexes with immunoglobulin G (IgG) and IgM antibodies.

Complement C3

An innate immune protein at the centre of the alternative and classical complement pathways.

Membrane attack complexes

Groups of proteins that are formed of complement components C8 and C9 that form pores in the membranes of microorganisms.

Complement system

An innate immune defence that recognizes and kills microorganisms through opsonization and formation of membrane attack complexes.

Opsonization

The process by which host molecules bind to the surface of a microorganism to enhance phagocytosis.

Outer membrane vesicle

A membrane-bound vesicle that is secreted from the bacterial envelope and can contain a variety of cellular material.

Mosaic alleles

Gene alleles that are produced by recombination of different gene sequences.

Multilocus sequence typing

A system to define strains of a species by defining the DNA sequence of alleles of a defined series of housekeeping genes.

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Quillin, S., Seifert, H. Neisseria gonorrhoeae host adaptation and pathogenesis. Nat Rev Microbiol 16, 226–240 (2018). https://doi.org/10.1038/nrmicro.2017.169

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