Related Experiment Videos
High mutation frequencies among Escherichia coli and Salmonella pathogens
1Molecular Biology Branch, Center for Food Safety and Applied Nutrition (HFS-235), Food and Drug Administration, Washington, DC 20204, USA. tac@vax8.cfsan.fda.gov
Abstract:
Here it is reported that the incidence of mutators among isolates of pathogenic Escherichia coli and Salmonella enterica is high (over 1 percent). These findings counter the theory, founded on studies with laboratory-attenuated strains, that suggests mutators are rare among bacterial populations. Defects in methyl-directed mismatch repair underlie all mutator phenotypes described here. Of nine independently derived hypermutable strains, seven contained a defective mutS allele. Because these mutant alleles increase the mutation rate and enhance recombination among diverse species, these studies may help explain both the rapid emergence of antibiotic resistance and the penetrance of virulence genes within the prokaryotic community.
Insights
Mutator bacteria, which have high mutation rates, are common in pathogenic Escherichia coli and Salmonella enterica. Defects in DNA mismatch repair, particularly in the mutS gene, cause these hypermutable strains, potentially explaining antibiotic resistance and virulence.
Area of Science:
- Microbiology
- Genetics
- Evolutionary Biology
Background:
- Mutator strains, bacteria with elevated mutation rates, were previously thought to be rare in natural populations based on studies of laboratory-attenuated strains.
- Pathogenic bacteria like Escherichia coli and Salmonella enterica are crucial targets for understanding microbial evolution and adaptation.
Purpose of the Study:
- To investigate the incidence and underlying genetic mechanisms of mutator phenotypes in pathogenic bacterial isolates.
- To determine if mutators are prevalent in pathogenic Escherichia coli and Salmonella enterica populations.
- To explore the implications of mutator prevalence for bacterial evolution, antibiotic resistance, and virulence.
Main Methods:
- Isolation and characterization of pathogenic Escherichia coli and Salmonella enterica strains.
- Assessment of mutation rates in bacterial isolates to identify hypermutable strains (mutators).
- Genetic analysis to identify mutations in key DNA repair genes, specifically focusing on methyl-directed mismatch repair pathways and the mutS gene.
Main Results:
- A high incidence of mutators (over 1%) was observed among isolates of pathogenic Escherichia coli and Salmonella enterica.
- Defects in the methyl-directed mismatch repair system were identified as the cause of all observed mutator phenotypes.
- Seven out of nine independently derived hypermutable strains possessed a defective mutS allele, indicating its significant role in generating mutator phenotypes.
Conclusions:
- Mutators are not rare but are highly prevalent in pathogenic bacterial populations, challenging previous assumptions.
- Mutations in mismatch repair genes, such as mutS, are the primary drivers of hypermutability in these pathogens.
- The increased mutation rate and enhanced recombination associated with mutator strains may accelerate the emergence of antibiotic resistance and the acquisition of virulence factors, impacting microbial evolution and public health.