Phase variation and adaptation in bacteria: a 'Red Queen's Race'

Abstract

In nature, bacteria are constantly exposed to many stressful conditions of life. This is particularly true of pathogens. Survival and adaptation under stressful conditions demand multiple strategies, genetic as well as phenotypic. Bacteria have many, pre-programmed, phenotypic stress response systems which can handle a limited number of stresses. Genetically, heritable as well as transient hypermutability mechanisms have been found to facilitate bacterial adaptation to varied and unpredictable stresses; these processes are not reviewed here. Instead, this article will focus on processes which do not increase global mutation rates but cause localized hypermutability in specific loci called contingency genes which have been identified particularly in pathogenic bacteria. These processes are collectively called phase and antigenic variations. Most of the contingency genes are involved in the synthesis or modification of surface-associated structures and enzymes. Phase variation in these genes involves high frequency, reversible, switching of their expression (on to off and off to on). The mechanisms of this switching are reviewed. However, some phase variable genes are not involved in the synthesis or modification of surface structures but are components of type I and type III restriction-modification (RM) systems. The on/off switching of these genes (type III RM genes) leads to regulation of expression of many unlinked genes, impacting several properties of cells. This novel type of control of multiple gene expression by phase variation has been named 'phasevarion'. The adaptive advantages of phase variation in contingency genes and phasevarions in the evasion of host immunity, virulence, niche adaptation and other phenomena are reviewed with some illustrative examples. Phase variation and bacterial adaptation have been likened to the 'Red Queen's Race' in Lewis Carrol's classic Through the Looking Glass.