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Proteomics of Neisseria Gonorrhoeae: The Treasure Hunt for Countermeasures Against an Old Disease

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Review

Proteomics of Neisseria Gonorrhoeae: The Treasure Hunt for Countermeasures Against an Old Disease

Benjamin I Baarda et al. Front Microbiol.

Abstract

Neisseria gonorrhoeae is an exquisitely adapted, strictly human pathogen and the causative agent of the sexually transmitted infection gonorrhea. This ancient human disease remains a serious problem, occurring at high incidence globally and having a major impact on reproductive and neonatal health. N. gonorrhoeae is rapidly evolving into a superbug and no effective vaccine exists to prevent gonococcal infections. Untreated or inadequately treated gonorrhea can lead to severe sequelae, including pelvic inflammatory disease and infertility in women, epididymitis in men, and sight-threatening conjunctivitis in infants born to infected mothers. Therefore, there is an immediate need for accelerated research toward the identification of molecular targets for development of drugs with new mechanisms of action and preventive vaccine(s). Global proteomic approaches are ideally suited to guide these studies. Recent quantitative proteomics (SILAC, iTRAQ, and ICAT) have illuminated the pathways utilized by N. gonorrhoeae to adapt to different lifestyles and micro-ecological niches within the host, while comparative 2D SDS-PAGE analysis has been used to elucidate spectinomycin resistance mechanisms. Further, high-throughput examinations of cell envelopes and naturally released membrane vesicles have unveiled the ubiquitous and differentially expressed proteins between temporally and geographically diverse N. gonorrhoeae isolates. This review will focus on these different approaches, emphasizing the role of proteomics in the search for vaccine candidates. Although our knowledge of N. gonorrhoeae has been expanded, still far less is known about this bacterium than the closely related N. meningitidis, where genomics- and proteomics-driven studies have led to the successful development of vaccines.

Keywords: Neisseria gonorrhoeae; antibiotic resistance; drugs; gonorrhea; molecular targets; proteomics; surveillance; vaccine.

Figures

FIGURE 1
FIGURE 1
A treasure hunt map of proteomic approaches applied to better understand GC pathophysiology and discovery of vaccine and drug targets. (A) Comparative proteome maps have been constructed between spectinomycin resistant (SpR) and spectinomycin sensitive (wild type; wt) GC isolates using 2-D-SDS-PAGE. (B) Proteomic investigations (1D SDS-PAGE and ICAT) of manganese (Mn) regulation of virulence factors and oxidative stress. (C) Proteomic profiling of GC transition from planktonic to biofilm growth using SILAC. (D) Comparative, high-throughput proteomic analyses of cell envelope and MV fractions derived from GC strains FA1090, F62, MS11, and 1291.

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