DNA Repair and Mutators: Effects on Antigenic Variation and Virulence of Bacterial Pathogens

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Abstract
This chapter discusses methyl-directed mismatch repair (MMR) mutators in the context of the evolution of bacterial pathogens. It is inevitable that any discussion of bacterial evolution ultimately focuses on mutation rate. Errors introduced by the DNA polymerase are circumvented both by its proofreading function and by the various DNA repair enzymes, primarily the MMR system, which monitor and repair lesions in the DNA. This underscores why DNA repair is essential to any discussion of bacterial evolution. The chemostat studies, as well as two independent reports that detected mutators among hospital isolates of Escherichia coli, suggested that mutators could persist in natural populations of bacteria. The authors have proposed that the persistence of mutator alleles in nature is the consequence of selection for new gene functions gained from promiscuous exchange, since the mutators observed are notably MMR- phenotypes. The roles that MutS, MutH, MutL, or UvrD deficiency play in the development of antigenic variation and virulence may be even more varied and subtle, due to the multiple ways these mutator phenotypes are expressed and act to affect gene structure.