Phytochemicals as Therapeutic Agents for ESKAPE Pathogens

Background: The worldwide increase of antimicrobial resistance in ESKAPE pathogens, which includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp., constitutes a substantial public health hazard, constraining treatment alternatives and elevating morbidity and mortality rates. As traditional antibiotics diminish in efficacy, phytochemicals are capturing interest due to their varied antibacterial characteristics and decreased susceptibility to developing antibiotic resistance. Phytochemicals, such as alkaloids, terpenes, phenolics, flavonoids, and organosulfur compounds, have multi-target processes that might provide innovative strategies for addressing infections caused by ESKAPE pathogens. Objective: The investigation sought to evaluate the effectiveness and mechanisms via which different phytochemicals could hinder and destroy the resistance pathways of ESKAPE bacteria, emphasizing their potential to serve as therapeutic agents in combating antimicrobial resistance. Results: Investigation demonstrates that some phytochemicals may disrupt many bacterial functions, such as cell wall production, membrane integrity, quorum sensing, and biofilm development in ESKAPE pathogens. For example, carvacrol from essential oils has shown efficacy against S. aureus by reducing staphyloxanthin synthesis and altering regulatory proteins, including SarA. Furthermore, conessine has altered resistance in A. baumannii by inhibiting the AdeIJK efflux pump. Flavonoids like resveratrol and curcumin have shown synergistic benefits with conventional antibiotics by improving their effectiveness while minimizing toxicity. These chemicals address several resistance pathways, impairing the ability of infections to build resistance. Conclusion: Phytochemicals provide an opportunity to facilitate the development of novel therapies targeting antimicrobial resistance in ESKAPE bacteria. Extensive efficacy and distinctive multi-target mechanisms of phytochemicals provide them promising candidates for combination therapy, possibly reinstating antibiotic effectiveness and decelerating the development of resistance. Additional investigation into the increase of bioavailability and clinical usage is essential to fully exploring the medicinal potential of phytochemicals.