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Published on: October 29, 2020
Revealing Insights into Natural Products Against mcr-1-Producing Bacteria
Ana Beatriz Souza Flor Dos Santos1, Manuele Figueiredo da Silva1, João Xavier de Araújo-Júnior1
1Laboratory of Medicinal Chemistry, Federal University of Alagoas, AC. Simoes Campus, Lourival Melo Mota Avenue 57072-970, Maceio, Brazil.
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.
Insights
Natural compounds show promise in combating Gram-negative bacterial resistance, specifically against the mcr-1 gene. These agents offer new therapeutic strategies for polymyxin-resistant infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Bacterial resistance, particularly in Gram-negative bacteria, is a significant global health threat.
- The mcr-1 gene confers resistance to polymyxins (colistin, polymyxin B), critical last-resort antibiotics.
- mcr-1 gene-mediated resistance has spread rapidly from animals to humans worldwide.
Purpose of the Study:
- To review natural compounds with activity against mcr-1 gene-mediated resistance.
- To explore the potential of natural agents as alternatives or adjuncts to existing antibiotic therapies.
- To highlight synergistic effects and molecular interactions of natural compounds with bacterial resistance mechanisms.
Main Methods:
- Literature review of studies on natural compounds and mcr-1 resistance.
- Analysis of synergistic activity of colistin with other compounds (e.g., azidothymidine, isoalantholactone).
- Evaluation of molecular docking studies for natural compounds (osthole, eugenol) targeting MCR-1 enzyme.
Main Results:
- Azidothymidine and isoalantholactone demonstrated synergistic activity with colistin.
- Paenipeptin 1 analog showed efficacy when combined with other antibiotics.
- Osthole and eugenol showed potential to inhibit the MCR-1 enzyme through molecular interactions.
Conclusions:
- Natural compounds represent a promising avenue for developing new pharmacotherapies against mcr-1-positive bacterial infections.
- Synergistic combinations of natural agents and existing antibiotics can overcome resistance.
- Further research into natural agents could lead to effective treatments for challenging Gram-negative infections.
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