Revisiting the Metallo-β-Lactamase-Mediated Antibiotic Resistance: Exploring Novel Mechanisms and Therapeutic...

Area of Science:

• Microbiology and Infectious Diseases
• Biochemistry and Enzymology
• Pharmacology and Therapeutics

Background:

• β-Lactam resistance, driven by β-lactamase enzymes, poses a significant global health challenge.
• Metallo-β-lactamases (MβLs) are a critical subclass, hydrolyzing a broad spectrum of β-lactam antibiotics, including carbapenems, and requiring zinc for activity.
• MβLs are classified into B1, B2, and B3 classes, each exhibiting unique substrate specificities and resistance mechanisms.

Purpose of the Study:

• To review the current landscape of MβL-mediated resistance, focusing on prevalent acquired MβLs (e.g., IMP, VIM, NDM).
• To highlight the challenges in MβL treatment, including antibiotic toxicity and co-resistance mechanisms (efflux pumps, porin modifications).
• To emphasize the critical need for innovative therapeutic and diagnostic strategies, including theranostics, for effective MβL infection management.

Main Methods:

• Literature review synthesizing current knowledge on MβL classification, resistance mechanisms, and clinical implications.
• Analysis of emerging therapeutic approaches and diagnostic advancements for MβL-producing bacteria.
• Discussion of the role of antimicrobial stewardship and global surveillance in combating MβL resistance.

Main Results:

• Acquired MβLs like IMP, VIM, and NDM are increasingly prevalent, necessitating novel treatment strategies.
• Existing treatment options are often complicated by antibiotic toxicity and the presence of co-existing resistance mechanisms.
• Rapid diagnostic advancements are crucial for timely identification of MβL-producing bacteria, guiding treatment selection and antimicrobial stewardship.

Conclusions:

• There is an urgent need for global collaborative efforts to address MβL-mediated resistance.
• Innovative therapies, particularly theranostic approaches, hold significant promise for managing MβL infections.
• Continued surveillance, advanced diagnostics, and development of novel treatments are paramount to combatting the threat of MβLs.