Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery

Yongqiang Yang; Yu-Hang Yan; Christopher J Schofield; Alan McNally; Zhiyong Zong; Guo-Bo Li

doi:10.1016/j.tim.2023.01.013

Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery

Yongqiang Yang, Yu-Hang Yan, Christopher J Schofield, Alan McNally, Zhiyong Zong^*, Guo-Bo Li^*

^*Corresponding author for this work

Microbiology and Infection

Research output: Contribution to journal › Review article › peer-review

Abstract

Resistance to β-lactam antibiotics is rapidly growing, substantially due to the spread of serine-β-lactamases (SBLs) and metallo-β-lactamases (MBLs), which efficiently catalyse β-lactam hydrolysis. Combinations of a β-lactam antibiotic with an SBL inhibitor have been clinically successful; however, no MBL inhibitors have been developed for clinical use. MBLs are a worrying resistance vector because they catalyse hydrolysis of all β-lactam antibiotic classes, except the monobactams, and they are being disseminated across many bacterial species worldwide. Here we review the classification, structures, substrate profiles, and inhibition mechanisms of MBLs, highlighting current clinical problems due to MBL-mediated resistance and progress in understanding and combating MBL-mediated resistance.

Original language	English
Journal	Trends in Microbiology
DOIs	https://doi.org/10.1016/j.tim.2023.01.013
Publication status	E-pub ahead of print - 27 Feb 2023

Bibliographical note

Keywords

antimicrobial resistance
β-lactam
metallo-β-lactamase
inhibitor classification
inhibition mechanism

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title = "Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery",

abstract = "Resistance to β-lactam antibiotics is rapidly growing, substantially due to the spread of serine-β-lactamases (SBLs) and metallo-β-lactamases (MBLs), which efficiently catalyse β-lactam hydrolysis. Combinations of a β-lactam antibiotic with an SBL inhibitor have been clinically successful; however, no MBL inhibitors have been developed for clinical use. MBLs are a worrying resistance vector because they catalyse hydrolysis of all β-lactam antibiotic classes, except the monobactams, and they are being disseminated across many bacterial species worldwide. Here we review the classification, structures, substrate profiles, and inhibition mechanisms of MBLs, highlighting current clinical problems due to MBL-mediated resistance and progress in understanding and combating MBL-mediated resistance.",

keywords = "antimicrobial resistance, β-lactam, metallo-β-lactamase, inhibitor classification, inhibition mechanism",

author = "Yongqiang Yang and Yu-Hang Yan and Schofield, {Christopher J} and Alan McNally and Zhiyong Zong and Guo-Bo Li",

year = "2023",

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day = "27",

doi = "10.1016/j.tim.2023.01.013",

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T1 - Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery

AU - Yang, Yongqiang

AU - Yan, Yu-Hang

AU - Schofield, Christopher J

AU - McNally, Alan

AU - Zong, Zhiyong

AU - Li, Guo-Bo

PY - 2023/2/27

Y1 - 2023/2/27

N2 - Resistance to β-lactam antibiotics is rapidly growing, substantially due to the spread of serine-β-lactamases (SBLs) and metallo-β-lactamases (MBLs), which efficiently catalyse β-lactam hydrolysis. Combinations of a β-lactam antibiotic with an SBL inhibitor have been clinically successful; however, no MBL inhibitors have been developed for clinical use. MBLs are a worrying resistance vector because they catalyse hydrolysis of all β-lactam antibiotic classes, except the monobactams, and they are being disseminated across many bacterial species worldwide. Here we review the classification, structures, substrate profiles, and inhibition mechanisms of MBLs, highlighting current clinical problems due to MBL-mediated resistance and progress in understanding and combating MBL-mediated resistance.

AB - Resistance to β-lactam antibiotics is rapidly growing, substantially due to the spread of serine-β-lactamases (SBLs) and metallo-β-lactamases (MBLs), which efficiently catalyse β-lactam hydrolysis. Combinations of a β-lactam antibiotic with an SBL inhibitor have been clinically successful; however, no MBL inhibitors have been developed for clinical use. MBLs are a worrying resistance vector because they catalyse hydrolysis of all β-lactam antibiotic classes, except the monobactams, and they are being disseminated across many bacterial species worldwide. Here we review the classification, structures, substrate profiles, and inhibition mechanisms of MBLs, highlighting current clinical problems due to MBL-mediated resistance and progress in understanding and combating MBL-mediated resistance.

KW - antimicrobial resistance

KW - β-lactam

KW - metallo-β-lactamase

KW - inhibitor classification

KW - inhibition mechanism

U2 - 10.1016/j.tim.2023.01.013

DO - 10.1016/j.tim.2023.01.013

M3 - Review article

C2 - 36858862

SN - 0966-842X

JO - Trends in Microbiology

JF - Trends in Microbiology

ER -

Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery

Abstract

Bibliographical note

Keywords

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