Mutators and hypermutability in bacteria: the Escherichia coli paradigm

Abstract

Mutators (also called hypermutators) are mutants which show higher than normal spontaneous mutation frequencies, ranging from 10-20 fold to 100-1000 fold higher, or sometimes even more, than wild-type cells. Being a mutator is advantageous to the organism when adapting to environmental changes or stressful situations, such as moving from one habitat to another, one host to another, exposure to antibiotics etc. However, this advantage is only a short-term benefit. In the long run, hypermutability leads to a fitness disadvantage due to accumulation of deleterious mutations or antagonistic pleiotropy or both. Contrary to intuitive expectations, hypermutability is commonly encountered in natural bacterial populations, especially among clinical isolates. It is believed to be involved in the emergence of antibiotic resistance and a hindrance to the treatment of infectious diseases. Here, I review the state of knowledge on the common mechanisms of hypermutability such as errors/defects in DNA replication, proof reading, mismatch repair, oxidative DNA damage, mistranslation etc., as well as phenomena associated with these processes, using Escherichia coli as a paradigmatic organism.