Identification and Characterization of Two Novel ISCR1-Associated Genes, dfrA42 and dfrA43, Encoding Trimethoprim-Resistant Dihydrofolate Reductases

Two novel ISCR1-associated dfr genes, dfrA42 and dfrA43, were identified from trimethoprim (TMP)-resistant Proteus strains and were shown to confer high levels of TMP resistance (MIC, ≥1,024 mg/liter) when cloned into Escherichia coli isolates. These genes were hosted by complex class 1 integrons, s...

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Published inAntimicrobial agents and chemotherapy Vol. 65; no. 5
Main Authors Li, Ling, Zhang, Mengge, Wang, Wenjia, Xia, Ruirui, Ma, Yanan, Wei, Xin, Wang, Xinhua, Sun, Xiaomin, Xie, Xiaohong, Xie, Shiling, Wang, Mingyu, Xu, Hai
Format Journal Article
LanguageEnglish
Published 1752 N St., N.W., Washington, DC American Society for Microbiology 01.05.2021
Subjects
Mechanisms of Resistance
antimicrobial resistance gene
inhibitor binding
trimethoprim
enzymatic parameter
mechanism of resistance
integron
dihydrofolate reductase
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Summary:Two novel ISCR1-associated dfr genes, dfrA42 and dfrA43, were identified from trimethoprim (TMP)-resistant Proteus strains and were shown to confer high levels of TMP resistance (MIC, ≥1,024 mg/liter) when cloned into Escherichia coli isolates. These genes were hosted by complex class 1 integrons, suggesting their potential for dissemination. Analyses of enzymatic parameters and TMP affinity were performed, and the results suggested that the mechanism of TMP resistance for these novel dihydrofolate reductases (DHFRs) is the reduction of binding with TMP.
Bibliography:Citation Li L, Zhang M, Wang W, Xia R, Ma Y, Wei X, Wang X, Sun X, Xie X, Xie S, Wang M, Xu H. 2021. Identification and characterization of two novel ISCR1-associated genes, dfrA42 and dfrA43, encoding trimethoprim-resistant dihydrofolate reductases. Antimicrob Agents Chemother 65:e02010-20. https://doi.org/10.1128/AAC.02010-20.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.02010-20