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Infection and Immunity, August 2008, p. 3700-3709, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00265-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Lotisha E. Garvin,¹ Margaret C. Bash,^2,3 Christine Keys,⁴ Douglas M. Warner,^1, Sanjay Ram,⁵ William M. Shafer,^6,7 and Ann E. Jerse^1*

Department of Microbiology and Immunology,¹ Department of Pediatrics, F. Edward Hèbert School of Medicine, Uniformed Services University, Bethesda, Maryland,² Division of Bacterial, Allergenic, and Parasitic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland,³ Division of Microbiological Studies, Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, Maryland,⁴ Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts,⁵ Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia,⁶ Laboratories of Microbial Pathogenesis, VA Medical Research Service, Veterans Affairs Medical Center, Decatur, Georgia⁷

Received 25 February 2008/ Returned for modification 19 April 2008/ Accepted 28 May 2008

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, β-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.

Published ahead of print on 9 June 2008.

Editor: A. Camilli

Present address: Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, Boston, MA.