Revealing Insights into Natural Products Against mcr-1-Producing Bacteria

Abstract

Bacterial resistance has become a major global concern, affecting about 500, 000 individuals in 22 countries. Thus, it is clear that Gram-negative bacteria have been receiving more attention in this scenario. These bacteria perform several resistance mechanisms, such as modifying lipid A from lipopolysaccharides as a product of the mcr-1 gene expression. This gene was initially identified in animals; however, it quickly spread to humans, spreading to 70 countries. Mcr-1 gene attributes resistance to polymyxin B and colistin, which are drugs established as the last alternative to combat Enterobacteriaceae bacteria. Notwithstanding the prevalence and lack of antibiotic therapies for such bacteria, this article aimed to compile information about natural compounds against the resistance attributed by this gene, including the activity of isolated colistin or its associations with other antibiotics. Among the studies that evaluated colistin's synergistic action with other compounds, azidothymidine and isoalantholactone stood out. On the other hand, the paenipeptin 1 analog showed satisfactory activities when associated with other antibiotics. Besides, it is worth mentioning that molecular docking results between ostole and eugenol toward phosphoethanolamine transferase MCR-1 revealed that these compounds could interact with critical amino acid residues for the catalytic action of this enzyme. Based on this, natural agents' role is evident against infections caused by mcr-1-positive bacteria, directly contributing to the development of new effective pharmacotherapies.