Hypermutable or mutator microorganisms are those that have an increased 
spontaneous mutation rate as a result of defects in DNA repair or error 
avoidance systems. Over the last two decades, several studies have provided 
strong evidence for a relevant role of mutators in the evolution of natural 
bacterial populations, particularly in the field of infectious diseases. Among 
them, chronic respiratory infection with Pseudomonas aeruginosa in cystic 
fibrosis (CF) patients was the first natural environment to reveal the high 
prevalence and important role of mutators. A remarkable positive selection of 
mutators during the course of the chronic infection has been reported, mainly as 
a result of the emergence of DNA mismatch repair system (mutS, mutL or 
mutU)-deficient mutants, although strains defective in the GO system (mutM, mutY 
and mutT) have also been observed. High frequencies of mutators have also been 
noted among other pathogens in the CF setting, particularly Staphylococcus 
aureus and Haemophilus influenzae. Enhanced antimicrobial resistance development 
is the most thoroughly studied consequence of mutators in CF and other chronic 
infections, although recent studies show that mutators may additionally have 
important effects on the evolution of virulence, genetic adaptation to the 
airways of CF patients, persistence of colonization, transmissibility, and 
perhaps lung function decline. Further prospective clinical studies are 
nevertheless still needed for an in-depth evaluation of the impact of mutators 
on disease progression and outcome.