Genetic mechanisms of bacterial antigenic variation.

The ability of an organism to respond and adapt to the environment is the keystone to its survival as a species. Pathogenic microorganisms have evolved a variety of mechanisms to deal with the rigors of the host immune response. These mechanisms, depending on the life cycle of the pathogen, include mimicry of host antigens, survival within professional phagocytes, and antigenic variation of major surface antigens (see reference 7). Not surprisingly, many pathogenic microbes which are constantly exposed to antibodies within the host have evolved the latter mechanism to deal with the immune response. The purpose of this article is to discuss in detail the genetic mechanisms of bacterial antigenic variation. For a review on antigenic variation of the African trypanosomes, we refer the reader to Borst and Cross (8). Broadly defined, antigenic variation refers to the ability of a microbe to alter the antigenic character of its surface components. The ability of a microbe to undergo antigenic variation is defined here as the ability of a single strain to express several antigenic variants of a cellular component, with the rate of change of the component being significantly higher than the mutation rate. The simplest form of antigenic variation involves a biphasic transition resulting from a rapid on-and-off switching of gene expression modulated by recombination at the deoxyribonucleic acid (DNA) level. Such switches occur for the type 1 pili of Escherichia coli (1), pilin of Neisseria gonorrhoeae (66, 69), and protein II (P.11) of N. gonorrhoeae (75). Some bacteria alternately express only two antigenic types of one protein. Salmonella typhimurium, the best-studied example, alternately expresses two flagellin genes, Hi and H2. Differential expression of Hi and H2 (also known as the flagellar phase transition) is controlled at the DNA level, involving an invertible segment of DNA, a