The "emerging pathogen" problem illustrates that microbes are not static but rather changing constantly and adapting to new niches. To investigate one possible molecular basis for this observed genetic variation, we measured the spontaneous mutation frequency in strains of recently isolated bacterial pathogens. Cultures of outbreak strains from collections of Escheaichia coli serotypes 0157:H7 and 055 and from Salmonella serovars were screened by assessing the frequency of mutants resistant to the antibiotics rifampicin, spectinomycin, and nalidixic acid. A high incidence (2.6%) of hypermutable strains (mutators) was found among these isolates. Genetic complementation analyses revealed that defects in methyl-directed mismatch repair underlie all mutator phenotypes identified, seven mutants containing a defective mutS allele and two involving mutH and uvrD. Since these mutant alleles both increase the mutation rate and enhance recombination among diverse species, our studies may help explain rapid emergence of antibiotic resistance and the penetrance of virulence genes within the prokaryotic community.