4.6 Article

Antibiotic Toxicity Profiles of Escherichia coli Strains Lacking DNA Methyltransferases

Journal

ACS OMEGA
Volume 6, Issue 11, Pages 7834-7840

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsomega.1c00378

Keywords

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Funding

  1. National Natural Science Foundation of China [21927807, 91743201, 22021003]
  2. Ministry of Science and Technology of China [2018YFC1005003, Y9L10301]

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Researching the impact of DNA methyltransferase on antibiotic toxicity can help address antibiotic resistance issues. Our experiments showed that E. coli strains lacking DNA methyltransferase genes were more sensitive to antibiotics.
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 lambda Red 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 EC50 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 EC50 values were independent of the mechanism underlying each antibiotic's mechanistic action.

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