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. 2023 May 1;95(5):e02010-20.
doi: 10.1128/AAC.02010-20. Epub 2021 Feb 16.

Identification and characterization of two novel IS CR1-associated genes dfrA42 and dfrA43 encoding trimethoprim resistant dihydrofolate reductases

Ling Li  1 , Mengge Zhang  1 , Wenjia Wang  1 , Ruirui Xia  1 , Yanan Ma  1 , Xin Wei  1 , Xinhua Wang  2 , Xiaomin Sun  3 , Xiaohong Xie  4 , Shiling Xie  4 , Mingyu Wang  5 , Hai Xu  5
Affiliations

Identification and characterization of two novel IS CR1-associated genes dfrA42 and dfrA43 encoding trimethoprim resistant dihydrofolate reductases

Ling Li et al. Antimicrob Agents Chemother. .

Abstract

Two novel ISCR1-associated dfr genes, dfrA42 and dfrA43, were identified from trimethoprim (TMP)-resistant Proteus strains and were shown to confer high level TMP resistance (MIC ≥ 1024 mg/L) when cloned into Escherichia coli These genes were hosted by complex class 1 integrons suggesting their potentials for dissemination. Analysis of enzymatic parameters and TMP affinity were performed, suggesting that the mechanism of TMP resistance for these novel DHFRs is the reduction of binding with TMP.

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Figures

FIG 1
FIG 1
Genetic structures of two novel dfr genes and phylogenetic analysis of DHFRs. (A) Genetic structures of complex class 1 integrons. Gray and black arrows, antibiotic resistance genes (dfrA42 and dfrA43); white arrows, conserved genetic elements of complex class 1 integrons; accession numbers HQ386845 and HQ386844, respectively. (B) Phylogenetic analysis of DHFRs. Red boxes, DfrA42 and DfrA43. GenBank accession numbers are listed alongside protein names. Numbers at each node are bootstrap values. Bar, evolutionary distance.
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