Elucidation of critical chemical moieties of metallo-β-lactamase inhibitors and prioritisation of target metallo-β-lactamases

Abstract

The urgent demand for effective countermeasures against metallo-β-lactamases (MBLs) necessitates development of novel metallo-β-lactamase inhibitors (MBLIs). This study is dedicated to identifying critical chemical moieties within previously developed MBLIs, and critical MBLs should serve as the target in MBLI evaluations. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic literature analysis was conducted, and the NCBI RefSeq genome database was exploited to access the abundance profile and taxonomic distribution of MBLs and their variant types. Through the implementation of two distinct systematic approaches, we elucidated critical chemical moieties of MBLIs, providing pivotal information for rational drug design. We also prioritised MBLs and their variant types, highlighting the imperative need for comprehensive testing to ensure the potency and efficacy of the newly developed MBLIs. This approach contributes valuable information to advance the field of antimicrobial drug discovery.

Graphical Abstract

Keywords:

• Metallo-β-lactamase inhibitor
• chemical moiety
• metallo-β-lactamase variant type

Acknowledgements

We thank our colleagues, both past and present, at the National Leading Research Laboratory of Drug Resistance Proteomics, Myongji University, for sharing their insights into the concepts presented here.

Author contributions statement

JHL, S-GK and D-WK contributed to the genome database survey and analysis. JHL, S-GK, K-MJ, KS, HJ, D-WK, BCJ and SHL performed the literature search and article writing (original draft preparation). SHL contributed to the funding acquisition and supervision. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

None.

Additional information

Funding

This work was supported by research grants from the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Information and Communications Technology (MSIT; grant No. NRF-2017M3A9E4078014); and from the NRF funded by the MSIT (grant Nos. NRF-2021R1A2C3004826 and NRF-2022R1F1A1074068).