Abstract
Adaptation to the changing environmental conditions experienced within a host requires genetic diversity within a microbial population. Genetic diversity arises from mutations which occur due to DNA damage from exposure to exogenous environmental stresses or generated endogenously through respiration or DNA replication errors. As mutations can be deleterious, a delicate balance must be obtained between generating enough mutations for micro-evolution to occur while maintaining fitness and genomic integrity. Pathogenic microorganisms can actively modify their mutation rate to enhance adaptive micro-evolution by increasing expression of error-prone DNA polymerases or by mutating or decreasing expression of genes required for DNA repair. Strains which exhibit an elevated mutation rate are termed mutators. Mutators are found in varying prevalence in clinical populations where large-effect beneficial mutations enhance survival and are predominately caused by defects in the DNA mismatch repair (MMR) pathway. Mutators can facilitate the emergence of antibiotic resistance, allow phenotypic modifications to prevent recognition and destruction by the host immune system and enable switching to metabolic and cellular morphologies better able to survive in the given environment. This review will focus on recent advances in understanding the phenotypic and genotypic changes occurring in MMR mutators in both prokaryotic and eukaryotic pathogens.
Highlights
The evolutionary success of pathogenic microorganisms is governed by their capacity to deal with environmental stress and rapidly adapt to the changing conditions experienced within the host
Microorganisms rely on mutations to produce novel genetic variation to enable them to survive and adapt to rapidly changing environments
It is becoming apparent that mutators present in clinical populations of pathogenic microbes can enhance adaptive evolution when a population encounters an environment where large-effect beneficial mutations exist to enhance survival
Summary
The evolutionary success of pathogenic microorganisms is governed by their capacity to deal with environmental stress and rapidly adapt to the changing conditions experienced within the host. Stress-induced mutagenesis occurs when cells actively modify the mutation rate through increasing expression of error-prone DNA polymerases or by mutating or decreasing expression of genes required for DNA repair [4] Pathogenic microorganisms can actively modify their mutation rate to enhance adaptive micro-evolution by increasing expression of error-prone DNA polymerases or by mutating or decreasing expression of genes required for DNA repair. Upon changing conditions within the host natural selection ensues cells possessing beneficial mutations (cream-colored cell) become predominant in the population in a short time frame in the process of micro-evolution; (b) Micro-evolution is enhanced in populations containing mutators, cells which possess an elevated mutation rate, as there is higher genetic diversity within.
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