Emerging therapeutic drug targets in amino acid and protein biosynthesis pathways against ESKAPE and non-ESKAPE pathogens: a comprehensive review.

Overuse and misuse of antibiotics used for treating bacterial infections has resulted in ineffectiveness of the drugs and hence increase in the cases of antimicrobial resistance. This has precipitated to the need for research and development of novel strategies to target pathogenic microbes. ESKAPE pathogens include high priority pathogens such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae (sometimes K. aerogenes), Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species (e.g., E. cloacae) which are responsible for causing healthcare associated infections whereas non ESKAPE pathogens such as Escherichia coli and Mycobacterium tuberculosis contribute to community acquired infections. Hence, targeting enzymes involved in amino acid and protein biosynthesis pathways is one such strategy for growth inhibition of these pathogens. Amino acids and their products are essential for various functions such as bacterial survivability, pathogenicity, cell wall integrity, essential mineral acquisition from surrounding or inside pathogen and activation of transporters. This review details the amino acid and protein biosynthetic pathways in pathogenic bacteria along with efficacy and translational potential of various natural and synthetic antimicrobial molecules discovered and synthesized against enzymes of these pathways for combating bacterial growth. This review also highlights promising antibacterial molecules such as quercetin, pyrazinoic acid, mupirocin and enrofloxacin etc. which are at various phases of clinical trials and hold promise for treatment of bacterial infections. Lastly, the review also lists risks such as cytotoxicity, redundancy and metabolic bypass associated with these inhibitors and also proposes future strategies such as trojan horse and combination therapy to deal with the above issues.