In Vivo Evolution of CTX-M-215, a Novel Narrow-Spectrum β-Lactamase in an Escherichia coli Clinical Isolate Conferring Resistance to Mecillinam

Mengyun Yin; Guoping Hu; Zhen Shen; Chengli Fang; Xuefei Zhang; Dan Li; Yohei Doi; Yu Zhang; Minggui Wang; Qinglan Guo

doi:10.1128/AAC.00562-20

In Vivo Evolution of CTX-M-215, a Novel Narrow-Spectrum β-Lactamase in an Escherichia coli Clinical Isolate Conferring Resistance to Mecillinam

Antimicrob Agents Chemother. 2020 Oct 20;64(11):e00562-20. doi: 10.1128/AAC.00562-20. Print 2020 Oct 20.

Authors

Mengyun Yin^{1

2}, Guoping Hu³, Zhen Shen⁴, Chengli Fang^{5

6}, Xuefei Zhang^{1

2}, Dan Li^{1

2}, Yohei Doi⁷, Yu Zhang^{5

6}, Minggui Wang^#^{8

2}, Qinglan Guo^#^{8

2}

Affiliations

¹ Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
² Key Laboratory of Clinical Pharmacology of Antibiotics, National Heath Commission of the People's Republic of China, Shanghai, China.
³ WuXi AppTec Co., Ltd., Shanghai, China.
⁴ Department of Laboratory, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
⁵ The Key Laboratory of Synthetic Biology, Chinese Academy of Sciences, Shanghai, China.
⁶ CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.
⁷ Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
⁸ Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China mgwang@fudan.edu.cn qinglanguo@fudan.edu.cn.

^# Contributed equally.

Abstract

Here, we report a novel narrow-spectrum β-lactamase CTX-M-215 identified in an Escherichia coli clinical isolate in China and conferring high-level resistance to mecillinam but not to cefotaxime. CTX-M-215 differed from CTX-M-125, a CTX-M extended-spectrum β-lactamase (ESBL), by an N132D substitution, which decreased hydrolytic activities toward penicillins and cephalosporins except for mecillinam. High similarity was observed between CTX-M-215- and CTX-M-125-bearing plasmids, carried by different isolates in the same patient, indicating in vivo evolution of CTX-M-215 from CTX-M-125.

Keywords: CTX-M-type enzyme; N132D; cefotaxime; mecillinam; narrow-spectrum β-lactamase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amdinocillin
Anti-Bacterial Agents / pharmacology
China
Escherichia coli / genetics
Escherichia coli Infections* / drug therapy
Humans
Microbial Sensitivity Tests
Plasmids / genetics
beta-Lactamases* / genetics

Substances

Anti-Bacterial Agents
beta-Lactamases
Amdinocillin