Antibiotic Toxicity Profiles of Escherichia coli Strains Lacking DNA Methyltransferases

[Image: see text] Antibiotic-resistant bacteria are causing more antibiotic treatment failures. Developing new antibiotics and identifying bacterial targets will help to mitigate the emergence and reduce the spread of antibiotic resistance in the environment. We investigated whether DNA methyltransferase (MTase) can be an adjunct target for improving antibiotic toxicity. We used Escherichia coli as an example. The genes encoding DNA adenine MTase and cytosine MTase, dam and dcm, respectively, were separately knocked out using the λRed system in E. coli MG1655. MG1655 and the two knockout strains were separately exposed in 96-well plates to 20 antibiotics from five classes. The EC(50) values of almost all of the tested antibiotics were lower in the dam and dcm knockout lines than that of the control. Our statistical analysis showed that the variations observed in EC(50) values were independent of the mechanism underlying each antibiotic’s mechanistic action.