Neisseria gonorrhoeae, the causative agent of gonorrhea, exhibits high frequency phase and antigenic variation during the course of disease. Genetic variation serves to rapidly adapt the pathogen to the numerous mucosal sites colonized with respect to the expression of bacterial adhesins and invasins and also enables the organism to evade recognition by the innate and acquired immune responses of the host. The predominant genetic mechanism responsible for the variable expression of surface constituents of the organism involves the deletion or insertion of tandem DNA repeats in the structural genes for enzymes necessary for the synthesis of cell wall components. Using the outer-membrane protein encoding opa gene family as the paradigm, we have characterized the genetic mechanism responsible for variation (termed """"""""Illegitimate Recombination"""""""") in order to understand the host and environmental factors that enhance or repress phase and antigenic variation. A novel mechanism for controlling variation has been found, which operates through the post-replicative DNA repair capacity of the organism. An increased understanding of variation will help in the design and implementation of both novel therapeutic approaches and the requirements necessary for an effective vaccine.
