The importance of phylogenetic studies in the evolution of beta-lactamases: Tracing antimicrobial resistance in priority pathogens

Beta-lactams have long been the standard therapeutic strategy for combating bacterial infections. However, the increasing resistance to these antibiotics has become a growing concern. One of the primary contributors to bacterial resistance is the production of beta-lactamases (BLs), enzymes capable of hydrolyzing the beta-lactam ring of these antibiotics, rendering them ineffective. In response, several alternative therapeutic strategies have been tested, but their success rate has been limited, highlighting the need for further research in this domain. Thus, it is crucial to study the evolution of BLs and their variants, as well as their transmission dynamics. In addition, cryptic genetic variations (CGVs), which act as hidden reservoirs of potential future phenotypes of BLs, have received insufficient attention. Identifying CGVs could help pinpoint selective pressures to avoid to prevent the evolution of BLs. Unlike conventional reviews that focus on classes of BLs or their resistance mechanisms, this article emphasizes the evolutionary perspectives of BLs. We explore the role of phylogenetic analysis in understanding the rise of different BL variants and their evolution in response to different selective pressures and gene transfer events. Most importantly, this review underscores the evolution of BLs, particularly in the context of the priority pathogens listed by the World Health Organization.