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

Ling Li; Mengge Zhang; Wenjia Wang; Ruirui Xia; Yanan Ma; Xin Wei; Xinhua Wang; Xiaomin Sun; Xiaohong Xie; Shiling Xie; Mingyu Wang; Hai Xu

doi:10.1128/AAC.02010-20

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

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

Authors

Ling Li¹, Mengge Zhang¹, Wenjia Wang¹, Ruirui Xia¹, Yanan Ma¹, Xin Wei¹, Xinhua Wang², Xiaomin Sun³, Xiaohong Xie⁴, Shiling Xie⁴, Mingyu Wang⁵, Hai Xu⁵

Affiliations

¹ State Key Laboratory of Microbial Technology, Microbial Technology Institute, Shandong University, Qingdao, Shandong, China.
² Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Qingdao, Shandong, China.
³ Environmental Research Institute, Shandong University, Qingdao, Shandong, China.
⁴ Shandong Shtars Medical Technology Co., Ltd.
⁵ State Key Laboratory of Microbial Technology, Microbial Technology Institute, Shandong University, Qingdao, Shandong, China. wangmingyu@sdu.edu.cn haixu@sdu.edu.cn.

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.