Scientific Publications by FDA Staff

Infect Immun 2008 Aug;76(8):3700-9

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.

Garvin LE, Bash MC, Keys C, Warner DM, Ram S, Shafer WM, Jerse AE

Jerse, AE, Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20853 USA Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20853 USA Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Pediat, Bethesda, MD 20853 USA US FDA, Ctr Biol Evaluat & Res, Div Bacterial Allergen & Parasit Prod, Bethesda, MD USA US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, College Pk, MD USA Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA USA Vet Affairs Med Ctr, VA Med Res Serv, Labs Microbial Pathogensis, Decatur, GA 30033 USA

porB variable region (VR) typing 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 some porin sequences confer a selective advantage during infection and/or transmission. Alternatively, certain porin types may be a marker of strains that are successful due to factors unrelated to porin. In support of the first hypothesis, here we show urogenital tract isolates of the most common PIA VR types obtained over a 10 year period in Baltimore, Maryland 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 the most common VR types. In contrast, three porin-independent phenotypes, namely lactoferrin utilization, beta-lactamase production, and the multiple transferable resistance (Mtr) phenotype, segregated with PFGE cluster and not VR type. Combined data with another PIA strain collection showed a strong correlation between serum resistance and the most common VR types. Comparison of VR typing hybridization patterns and the nucleotide sequence of 12 porB1A genes suggests 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.