Role of Phase and Antigenic Variation in Neisseria gonorrhoeae Colonization

Phase-variable expression of different versions of the same gene, as in the case of opa genes, or of genes that contribute to the structure of the same macromolecule, as occurs with lipooligosaccharide (LOS) biosynthesis genes, results in reversible changes in the antigenic makeup of the bacterial surface. Pilin antigenic variation, the result of new genetic information recombining into the pilin gene, is perhaps the most fascinating example of true antigenic variation in Neisseria gonorrhoeae. Despite the experimental challenges inherent in studying this human-specific pathogen, evidence that variable expression of surface molecules plays a critical role in gonococcal pathogenesis is strong. The depth of variability created by the size of the pilin repertoire and the seemingly random manner by which cassettes are inserted make Neisseria pilus antigenic variation one of the most fascinating stories of genetic diversity in bacterial pathogenesis. The purpose of pilus phase variation in bacterial pathogenesis is less intuitive than that of antigenic variation. Experimental infection of mice may be a useful tool for investigating the kinetics of gonococcal opacity (Opa) expression in vivo. Recovery of Opa-positive variants occurs following vaginal inoculation of mice with a predominantly Opa-negative inoculum. Acquisition of iron for growth and as a cofactor of several key enzymes in the low-iron environment of the host is important for successful colonization by most microbes.