Redirecting Pantoprazole As a Metallo-beta-lactamase Inhibitor in Carbapenem-resistant

Overview

Journal Front Pharmacol

Date 2024 Mar 27

PMID 38533260

Authors

Wesam H Abdulaal

Nabil A Alhakamy

Amer H Asseri

Mohamed F Radwan

Tarek S Ibrahim

Solomon Z Okbazghi

Hisham A Abbas

Basem Mansour

Aly A Shoun

Wael A H Hegazy

Mahmoud Saad Abdel-Halim

Affiliations

Soon will be listed here.

Abstract

The development of resistance to carbapenems in due to the production of metallo-β-lactamases (MBLs) is a critical public health problem because carbapenems are the last-resort drugs used for treating severe infections of extended-spectrum β-lactamases (ESBLs) producing . Restoring the activity of carbapenems by the inhibition of metallo-β-lactamases is a valuable approach to combat carbapenem resistance. In this study, two well-characterized clinical multidrug and carbapenem-resistant isolates were used. The sub-inhibitory concentrations of pantoprazole and the well-reported metallo-β-lactamase inhibitor captopril inhibited the hydrolytic activities of metallo-β-lactamases, with pantoprazole having more inhibiting activities. Both drugs, when used in combination with meropenem, exhibited synergistic activities. Pantoprazole could also downregulate the expression of the metallo-β-lactamase genes and . A docking study revealed that pantoprazole could bind to and chelate zinc ions of New Delhi and Verona integron-encoded MBL (VIM) enzymes with higher affinity than the control drug captopril and with comparable affinity to the natural ligand meropenem, indicating the significant inhibitory activity of pantoprazole against metallo-β-lactamases. In conclusion, pantoprazole can be used in combination with meropenem as a new strategy for treating serious infections caused by metallo-β-lactamases producing .

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