MetQ of Neisseria gonorrhoeae Is a Surface-Expressed Antigen That Elicits Bactericidal and Functional Blocking Antibodies

Abstract

Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection (STI) gonorrhea, is a growing public health threat for which a vaccine is urgently needed. We characterized the functional role of the gonococcal MetQ protein, which is the methionine binding component of an ABC transporter system, and assessed its potential as a candidate antigen for inclusion in a gonococcal vaccine. MetQ has been found to be highly conserved in all strains investigated to date, it is localized on the bacterial surface, and it binds l-methionine with a high affinity. MetQ is also involved in gonococcal adherence to cervical epithelial cells. Mutants lacking MetQ have impaired survival in human monocytes, macrophages, and serum. Furthermore, antibodies raised against MetQ are bactericidal and are able to block gonococcal adherence to epithelial cells. These data suggest that MetQ elicits both bactericidal and functional blocking antibodies and is a valid candidate antigen for additional investigation and possible inclusion in a vaccine for prevention of gonorrhea.

Quantitative Proteomics of the 2016 WHO Neisseria gonorrhoeae Reference Strains Surveys Vaccine Candidates and Antimicrobial Resistance Determinants

“…The results of all software programs and the majority votes strategy revealed six additional CE proteins, four of which were found in the majority of examined strains (supplemental Table S6). In addition, literature searches for experimental evidence of protein surface exposure allowed assignment of BamE [NGO1780; (71)], SliC [NGO1063; (72)], MetQ [NGO2139; (30,73)], Ng-MIP [NGO1225; (30,74)], and BamG [NGO1985; (75)] to the cell surface. Subcellular location predictions for all proteins are listed in supplemental Table S8.…”

Quantitative proteomics of the 2016 WHONeisseria gonorrhoeaereference strains surveys vaccine candidates and antimicrobial resistance determinants

“…The results of all software programs and the majority votes strategy revealed six additional CE proteins, four of which were found in the majority of examined strains (Supplemental Table S6). In addition, literature searches for experimental evidence of protein surface exposure allowed assignment of BamE [NGO1780; (72)], SliC [NGO1063; (73)], MetQ [NGO2139; (30, 74)], Ng-MIP [NGO1225; (30, 75)], and BamG [NGO1985; (76)] to the cell surface.…”

“…In addition, Ng-MIP-like proteins exist in C. trachomatis , G. vaginalis , and P. ruminicola ; BamA and NGO1559 homologs were found in C. trachomatis and P. ruminicola . MetQ, a methionine transporter (74), was the only proteomics-derived vaccine candidate with homologs across all examined bacteria with the exception of C. trachomatis and P. ruminicola . Further, we detected protein homologs of PilQ in two C. trachomatis strains and MtrE and ZnuD in P. ruminicola ; these three proteins were absent in commensal species.…”

Genome-wide screening of lipoproteins in Actinobacillus pleuropneumoniae identifies three antigens that confer protection against virulent challenge

“…APJL_0922 encodes a protein with homology to d-methionine-binding lipoprotein MetQ of other bacteria. Previous studies have suggested that MetQ is involved in methionine transport, cell adherence, intracellular survival in Neisseria gonorrhoeae, and more importantly, the surface-located MetQ protein is a promising vaccine candidate that elicits bactericidal and functional blocking antibodies 38 . The A. pleuropneumoniae TolA protein is homologous to the colicin transporter of Neisseria sicca, and contains 15 copies of EAEAKAKA in the intragenic tandem repeat (TR) region at the N terminus, and is implicated in E. coli colicin uptake, filamentous phage infection, and detergent tolerance 39 .…”