Playing Dr Jekyll and Mr Hyde: combined mechanisms of phase variation in bacteria

Phase variation is the adaptive process by which bacteria undergo frequent and reversible phenotypic changes resulting from genetic alterations in specific loci of their genomes. This process is crucial for the survival of pathogens and commensals in hostile and ever-changing host environments. Despite important differences in the molecular mechanisms that mediate and regulate phase variation, related strategies have evolved to generate high levels of genetic diversity through complex and combinatorial reshuffling of genetic information. Recent studies, supported by the emergence of global genomic approaches, have revealed that bacterial pathogens often use a combination of different mechanisms to vary the expression of a variety of biological functions, providing new insights into bacterial adaptation and virulence mechanisms. Recent advances in the understanding of the molecular mechanisms of phase variation are reviewed, and differences in these mechanisms outlined.