ESKAPE pathogens and associated quorum sensing systems: New targets for novel antimicrobials development

Abstract

Globally, antimicrobial (AMR) or multi-drug resistance (MDR) constitutes a current health challenge that is predicted to cause increased infections rates with adverse socioeconomic impacts through increase in healthcare costs. In addition, the group of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. (ESKAPE) pathogens cause debilitating infections (community and nosocomial) and are classed as priority 1 AMR pathogens. This systematic report therefore aimed at providing detailed coverage of new targets for novel antimicrobials development against MDR ESKAPE pathogens to mitigate future AMR spread and improve current public health indices. The prevalent ESKAPE bacterial group show high resistance to quinolones, lactams, cephalosporins, carbapenems and other antibiotic groups, and ability to form biofilms linked to various quorum sensing systems (QSSs) that boost their virulence. These QS pathways have become viable targets in drug design efforts for new antimicrobials development. Also, since antibiotics discovery and development has waned in the past decade, the emergence of advanced computational modelling technologies in drug design, repurposing and development efforts may yet bridge the gap. As such, in this work we provided a comprehensive and systematic overview using relevant, included data and findings on ESKAPE pathogens, their QSSs to target for novel antimicrobial agents’ development, the contributions of computational tools at the heart of novel antimicrobial advancements and their roles in bioprospecting and developing novel ‘druggable’ candidates and therapies with anti-biofilm, and anti-quorum sensing activities to mitigate AMR, biofilm and QS-related pathogenicity factors.