Emerging Molecular Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens: A Comprehensive Review

The rise of antimicrobial resistance has marked ESKAPE pathogens as a serious global health threat, primarily due to the limitations and frequent failures of broad-spectrum antibiotic-based treatment. Moreover, the misuse and overuse of antibiotics have further complicated the management of bacterial infections by enhancing the risk of secondary infections. Despite traditional antibiotic development, there is a need for novel strategies to tackle the rising menace of ESKAPE pathogens. During the past few decades, various cellular and molecular-level investigations based on multidrug-resistant bacterial species have emerged. These investigations have played a major role in unraveling the intrinsic pathways that are involved in conferring AMR to ESKAPE pathogens. The molecular mechanisms of AMR in ESKAPE involve expression of efflux pumps, persistent biofilms, enzymatic drug inactivation, alterations in antibiotic targets, genetic mutations, and horizontal gene transfer. This review highlights the major molecular mechanisms of antimicrobial resistance in ESKAPE pathogens. By understanding these mechanistic pathways, more specific/targeted diagnostics and therapeutic approaches may be developed. This review outlines key findings from recent research studies on AMR trends in ESKAPE pathogens. This comprehensive review also provides current research gaps and future directions for combating AMR.