
Full text loading...
Category: Bacterial Pathogenesis
DNA Repair and Mutators: Effects on Antigenic Variation and Virulence of Bacterial Pathogens, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818111/9781555811747_Chap10-1.gif /docserver/preview/fulltext/10.1128/9781555818111/9781555811747_Chap10-2.gifAbstract:
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.
Full text loading...
Effect of defective MMR on the time frame for evolutionary change. Defects in the MMR pathway increase mutations from errors in DNA replication and repair and enhance recombination of diverged DNA among and between bacterial species. The increased rates of spontaneous mutation and homeologous recombination observed in MMR-defective strains suggest that MMR mutators may act to cause rapid evolutionary change.
Effect of defective MMR on the time frame for evolutionary change. Defects in the MMR pathway increase mutations from errors in DNA replication and repair and enhance recombination of diverged DNA among and between bacterial species. The increased rates of spontaneous mutation and homeologous recombination observed in MMR-defective strains suggest that MMR mutators may act to cause rapid evolutionary change.
Estimates of fidelity during the course of DNA replication. Bar graphs represent the additive effect of each step that controls the fidelity of DNA replication and show the decrease in error rate, given as error per DNA nucleotide replicated.
Estimates of fidelity during the course of DNA replication. Bar graphs represent the additive effect of each step that controls the fidelity of DNA replication and show the decrease in error rate, given as error per DNA nucleotide replicated.
Mutator loci in E. coli. Mutant loci that increase the spontaneous mutation rate are shown on the outside of the genetic map of E. coli. Preferential mutations induced in each mutant strain are given, except for the pleiotropic MMR mutators, which are highlighted in gray. Genetic loci shown inside the map are antibiotic resistance determinants used to screen the mutator phenotype (see text). The circular genetic map is shown with centisome intervals indicated for the 100-minute map and 1,000-kb (K) intervals indicated for the 4,639-kb genome.
Mutator loci in E. coli. Mutant loci that increase the spontaneous mutation rate are shown on the outside of the genetic map of E. coli. Preferential mutations induced in each mutant strain are given, except for the pleiotropic MMR mutators, which are highlighted in gray. Genetic loci shown inside the map are antibiotic resistance determinants used to screen the mutator phenotype (see text). The circular genetic map is shown with centisome intervals indicated for the 100-minute map and 1,000-kb (K) intervals indicated for the 4,639-kb genome.
Phenotypes associated with mutant strains carrying defects in the MMR pathway.
Phenotypes associated with mutant strains carrying defects in the MMR pathway.
Number of total, deleterious, lethal, and favorable mutations per genome, gene, and base pair replication
Number of total, deleterious, lethal, and favorable mutations per genome, gene, and base pair replication