E. coli dam strains, deficient in DNA methylation, have an active but non-directed mismatch repair system (MMRS) that can cause cell death by making double-strand breaks on unmethylated GATC sequences. Here we show that an increased level of MutS, -L or -H in E. coli dam cells enhances the mismatchstimulated cell killing, resulting in strains with an apparent reduced mutation frequency. These strains have a similar duplication time, percentage of live/dead cells and morphotype to that of the dam strain. These strains also showed an increased sensitivity to the base analogue 2-AP, confirming that they have a more active MMRS. Dam methylation also participates in transcriptional regulation of virulent genes in several bacterial species. Therefore, dam strains of some of these bacterial species are less virulent and are being tested as live vaccines to generate immune protection against the virulent wild-type bacteria. However, a nondesirable characteristic of these dam strains is that they are mutator. Our results suggest that this disadvantage can be considerably reduced increasing the level of MutS, -L or -H.
