Phenotypic and Genotypic Analyses of Neisseria gonorrhoeae Isolates That Express Frequently Recovered PorB PIA Variable Region Types Suggest that Certain P1a Porin Sequences Confer a Selective Advantage for Urogenital Tract Infection

Abstract

Typing of the porB variable region (VR) is an epidemiological tool that classifies gonococcal strains based on sequence differences in regions of the porB gene that encode surface-exposed loops. The frequent isolation of certain porB VR types suggests that some porin sequences confer a selective advantage during infection and/or transmission. Alternatively, certain porin types may be markers of strains that are successful due to factors unrelated to porin. In support of the first hypothesis, here we show urogenital tract isolates representing the most common PIA VR types identified in an urban clinic in Baltimore, MD, over a 10-year period belonged to several different clonal types, as determined by pulsed-field gel electrophoresis (PFGE). Serum resistance, which was confirmed by factor H and C4b-binding protein binding studies, was more often associated with gonococcal the most common VR types. In contrast, three porin-independent phenotypes, namely, lactoferrin utilization, ␤-lactamase production, and multiple transferable resistance (Mtr), were segregated with the PFGE cluster and not with the VR type. Data combined with another PIA strain collection showed a strong correlation between serum resistance and the most common VR types. A comparison of VR typing hybridization patterns and nucleotide sequences of 12 porB1a genes suggests that certain porin loop 1, 3, 6, and/or 7 sequences may play a role in the serum resistance phenotype. We conclude that some PorB PIA sequences confer a survival or transmission advantage in the urogenital tract, perhaps via increased resistance to complement-mediated killing. The capacity of some porin types to evade a porin-specific adaptive immune response must also be considered.

Functional Characterization of Antibodies against Neisseria gonorrhoeae Opacity Protein Loops

“…For assays that used strain FA1090 F62por5–8 , 1% NHS was used. These serum concentrations are >2-fold lower than that concentration that showed no killing of the target strains in the absence of added antibody as determined by Garvin et al [36]. For testing Opa loop-specific antibodies, Ab linear or Ab cyclic were serially diluted in minimal essential medium (MEM) (final volume 150 µl), and 50 µl of diluted NHS or BBS were added to each well to achieve the final serum concentrations stated above based on a final 250 µl volume.…”

Correlation between antibiotic susceptibilities and genotypes in Neisseria gonorrhoeae from different geographical origins: determinants monitoring by real-time PCR as a complementary tool for surveillance

“…The possible implication of porB1a sequence modifications in this decreased susceptibility is not elucidated. This allele is suspected to confer a survival or transmission advantage in the urogenital tract28 and to be more frequently responsible for invasive infections; their relatively high prevalence deserves consideration.…”

Proteomics-driven Antigen Discovery for Development of Vaccines Against Gonorrhea

“…Bacterial Strains and Growth Conditions-The following N. gonorrhoeae strains were used in this study: FA1090 (22), MS11 (23), 1291 (24), F62 (25), FA19 (26), the clinical isolates LGB1, LG14, LG20, and LG26, which were collected from two public health clinics in Baltimore from 1991 to 1994 and differ in porB variable region type and pulsed gel electrophoresis patterns (21,27), 13 isolates from patients attending the Public Health-Seattle & King County Sexually Transmitted Disease clinic from 2011 to 2013 (supplemental Table S1), and the WHO 2015 reference strains (10,28,29).…”