Polymorphisms in the rifampin resistance mutation frequency (f) were studied in 696 Escherichia coli strains from Spain, Sweden, and Denmark. Of the 696 strains, 23% were weakly hypermutable (4 ؋ 10 ؊8 < f < 4 ؋ 10 ؊7 ), and 0.7% were strongly hypermutable (f > 4 ؋ 10 ؊7 ). Weak mutators were apparently more frequent in southern Europe and in blood isolates (38%) than in urinary tract isolates (25%) and feces of healthy volunteers (11%).Microbial evolution is dependent on two opposing forces, the maintenance of genetic information and the generation of some suitable level of genetic variation on which selection can act. In most cases, genetic variation is assured by errors in DNA replication, determined by the accuracy of DNA polymerases and various DNA repair systems. Particular environmental characteristics will influence selection of the optimal amount of genetic variation for a given organism with a specific population structure. If the environment changes rapidly in time or is heterogeneous, variants with increased mutation rates will tend to be selected, since they have an increased probability of forming beneficial mutations. Conversely, if the environment is constant, as the organism becomes maximally adapted, mutation rates tend to decrease because of the costs associated with deleterious mutations (4, 6, 7). These considerations suggest that environment-dependent polymorphisms in mutation frequency can be expected in nature.Mutation frequencies were determined in a collection of 696 Escherichia coli strains obtained from 2000 to 2003. Of the 696 E. coli strains, 300 were from Spain (100 from positive urine cultures, 100 from blood cultures, and 100 from the stools of young healthy volunteers), 170 were from Denmark (blood cultures), and 226 were from Sweden (urinary tract cultures from outpatients). Each Luria-Bertani (LB) tube was inoculated with an independent colony obtained from a blood agar plate; three LB tubes were used. After 24 h of incubation, appropriate dilutions were seeded onto LB agar plates and LB agar plates containing rifampin (100 g/ml), and colony counts were performed after 24 or 48 h, respectively. Mutation frequencies are reported as a proportion of the number of rifampin-resistant colonies to the total viable count. The results corresponded to the mean value obtained in three independent experiments that were repeated in cases of suspected jackpots.Categories were established considering the distribution of frequencies of the 696 E. coli strains (Fig. 1). A strain was considered normomutable when the mutation frequency (f) was at or close to the modal point of the distribution of mutation frequencies; for practical purposes, it was established as 8 ϫ 10 Ϫ9 Ͻ f Ͻ 4 ϫ 10 Ϫ8 . Strains were considered weak mutators if their frequency was 4 ϫ 10 Ϫ8 Յ f Ͻ 4 ϫ 10 Ϫ7 and strong mutators if f Ն 4 ϫ 10 Ϫ7 . Hypomutable strains were defined as strains with f Յ 8 ϫ 10 Ϫ9 . A sharp peak in the frequency distribution was always found at 10 Ϫ8 . From this value, a few strains had lower mutatio...

Hypermutable (mutation frequency [f], >4 ؋ 10؊8 ) Escherichia coli strains were more frequently found (43%) in a collection of 89 extended-spectrum ␤-lactamase (ESBL)-producing isolates from different patients (77 pulsed-field gel electrophoresis clones, 12 ESBL types) than in non-ESBL E. coli (26%) strains (P ‫؍‬ 0.03). Among urinary tract isolates, the frequency of hypermutation was 40% in ESBL versus 26% in non-ESBL isolates (P ‫؍‬ 0.03).

No abstract

No abstract