Diversity and proliferation of metallo-β-lactamases : a clarion call for clinically effective metallo-β-lactamase inhibitors
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Date
Authors
Somboro, Anou M.
Osei Sekyere, John
Amoako, Daniel G.
Essack, Sabiha Y.
Bester, Linda A.
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology
Abstract
The worldwide proliferation of life-threatening metallo-β-lactamase (MBLs)-producing Gram-negative bacteria is a serious concern to public health. MBLs are compromising the therapeutic efficacies of β-lactams, particularly carbapenems, which are last-resort antibiotics indicated for various multidrug-resistant bacterial infections. Inhibiting enzymes mediating antibiotic resistance in bacteria is one of the major promising means in overcoming bacterial resistance. Compounds having potential MBLs-inhibitory activity have been reported, but none are currently under clinical trials. The need for developing safe and efficient MBL inhibitors (MBLIs) is obvious, particularly with the continuous spread of MBLs worldwide. In this review, the emergence and escalation of MBLs in Gram-negative bacteria are dicussed. The relationship between different class B β-lactamases identified up to 2017 are represented by a phylogenetic tree and summarized. On the other hand, approved and/or clinical-phase serine β-lactamase inhibitors are recapitulated to reflect the successful advances made in developing class A β-lactamase inhibitors. Reported MBLIs, their inhibitory properties and purported mode of inhibition are herein delineated. Insights into MBLs' structural variations and the challenges involved in developing potent MBLIs are also elucidated and discussed. Currently, natural products and MBL-resistant β-lactam analogues are the most promising agents that can become clinically efficient MBLIs. A deeper comprehension of the mechanism of action and activity spectrum of the various MBLs and their inhibitors will serve as a bedrock for further investigations that can result in clinically useful MBLIs to curb this global menace.
Description
Keywords
Antibiotic resistance, Gram-negative bacteria, Metallo-β-lactamase (MBLs), Metallo-β-lactamase inhibitors, β-lactam antibiotics, β-lactamase, Amides, Amino acid (AA), Antibiotics, Enzyme inhibition, Metals, Bacterial infections, Bacterial resistance, Lactamases, Multidrug-resistant (MDR), Structural variations, Therapeutic efficacy, Bacteria (microorganisms), Negibacteria
Sustainable Development Goals
Citation
Somboro AM, Osei Sekyere J, Amoako DG, Essack SY, Bester LA. 2018. Diversity and proliferation of metallo-β-lactamases: a clarion call for clinically effective metallo-β-lactamase inhibitors. Appl Environ Microbiol 84:e00698-18. https://doi.org/10.1128/AEM.00698-18.