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 spe cific loci of their genomes. This process is crucial for the survival of pa thogens and commensals in hostile and ever-changing host environments. Desp ite important differences in the molecular mechanisms that mediate and regu late phase variation, related strategies have evolved to generate high leve ls of genetic diversity through complex and combinatorial reshuffling of ge netic information. Recent studies, supported by the emergence of global gen omic approaches, have revealed that bacterial pathogens often use a combina tion of different mechanisms to vary the expression of a variety of biologi cal functions, providing new insights into bacterial adaptation and virulen ce mechanisms. Recent advances in the understanding of the molecular mechan isms of phase variation are reviewed, and differences in these mechanisms o utlined.