Phytochemicals as Potential Antibacterial Agents Against ESKAPE Pathogens

The alarming increase in antimicrobial resistance (AMR) phenomena becomes a serious global public health threat across the globe. Irrational use, misuse, and overprescription of antibiotics with non-specific purpose are the primary causes of AMR in pathogens. According to WHO, the priority pathogens, particularly ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp.), pose extensive resistance to several antibiotics leading to global health hazards. These pathogenic bacteria are associated with several chronic health conditions by producing pathogenic elements, development of biofilm dynamics, expressions of efflux pumps, and inference of AMR. Owing to the importance of bacterial virulence and biofilm dynamics in the occurrence of resistance to antibiotics in clinical healthcare settings, it is imperative to look for alternative therapeutic agents to mitigate bacterial pathogenesis and biofilm dynamics. In search of novel antibacterial and antibiofilm agents, several synthetic and semi-synthetic drugs are being considered for efficient management of chronic microbial diseases. Nevertheless, several factors such as biodegradability issues, toxicity, and less absorptivity limit their candidature as promising therapeutic agents against chronic bacterial infections. In this context, pharmacologically important medicinal plants with high-throughput values in folkloric practices could invariably be developed as therapeutic agents for the treatment of bacterial infections associated with ESKAPE pathogens. In recent years, several reports have emphasized the use of medicinal plants and plant-derived secondary metabolites against bacterial pathogenesis, biofilm mechanics, and drug resistance severity. The present chapter, thus, emphasizes the therapeutic role of phytochemicals in the development of antibacterial agents, inhibitors of quorum sensing- (QS) mediated bacterial pathogenesis, inhibitors of efflux machinery, and mitigators of biofilm matrices against ESKAPE group of microorganisms. The chapter also critically evaluates the FDA-approved phytochemical drugs and their formulations for therapeutic management of bacterial drug resistance. An interactive discussion also emphasizes the repurposing of FDA-approved phytochemicals towards the mitigation of bacterial infections and biofilms, which are being used earlier for other therapeutic roles. The chapter also focuses on combinatorial tactics using phytochemicals with existing antibiotics and phytochemicals-based nanoformulations to mitigate the severity of bacterial infections in ESKAPE pathogens.