Insights into biofilm-mediated mechanisms driving last-resort antibiotic resistance in clinical ESKAPE pathogens.

The rise of antibiotic-resistant bacteria poses a grave threat to global health, with the ESKAPE pathogens, which comprise , , , , and spp. being among the most notorious. The World Health Organization has reserved a group of last-resort antibiotics for treating multidrug-resistant bacterial infections, including those caused by ESKAPE pathogens. This situation calls for a comprehensive understanding of the resistance mechanisms as it threatens public health and hinder progress toward the Sustainable Development Goal (SDG) 3: Good Health and Well-being. The present article reviews resistance mechanisms, focusing on emerging resistance mutations in multidrug-resistant ESKAPE pathogens, particularly against last-resort antibiotics, and describes the role of biofilm formation in multidrug-resistant ESKAPE pathogens. It discusses the latest therapeutic advances, including the use of antimicrobial peptides and CRISPR-Cas systems, and the modulation of quorum sensing and iron homeostasis, which offer promising strategies for countering resistance. The integration of CRISPR-based tools and biofilm-targeted approaches provides a potential framework for managing ESKAPE infections. By highlighting the spread of current resistance mutations and biofilm-targeted approaches, the review aims to contribute significantly to advancing our understanding and strategies in combatting this pressing global health challenge.