Antibiotic resistance poses a global health challenge. Multiple resistance mechanisms enable bacterial pathogens to evade antibiotic killing. Furthermore, there is a lack of new antibiotics entering the clinical pipeline. An alternative strategy to alleviate the problem of antibiotic resistance is the use of antibiotic potentiators, also known as antibiotic adjuvants or resistance breakers. Antibiotic potentiators are molecules that may not have antibiotic activity on their own but are able to block the bacterial resistance mechanisms or enhance the antibacterial activity of antibiotics. As such, antibiotic potentiators are a promising approach to combat drug resistance in bacterial pathogens. This mini review aims to elaborate on the discovery and development of antibiotic potentiators for the past decade (2012-2022) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), an important nosocomial pathogen that is resistant to almost all β-lactam antibiotics. Different microbial-derived compounds and studies pertaining to their discovery process will be elucidated. The mechanisms by which these antibiotic potentiators exert their adjuvating activity and their targets will also be discussed.
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