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Antimicrobial Peptides: The Coming Age Therapeutics

by Sri Sindhu Bhatta

The prevalence of antibiotic-resistant bacteria is a result of the overuse of antibiotics in human and animal health. As per various National and International health agencies' data, this antibiotic resistance and multi-resistance prevalence is posing a major and increasing threat. Antibiotics lead to the broad-spectrum killing of bacteria and their routine usage as medicine since its discovery has served as the pivot to antimicrobial resistance in bacteria. Bacteria that cope with highly competitive environments have evolved various adaptive strategies over time. One such strategy is the production of narrow-spectrum antimicrobial peptides commonly known as Bacteriocins. These antimicrobial peptides are specifically called microcins in Gram-negative bacteria. The unique feature of bacteriocins being ‘narrow spectrum’ is being used to thwart the increasing threat of antibiotic resistance or multi-resistance in pathogenic bacteria.



One of the most pressing issues in the medical field for decades is antibiotic resistance. There

have been many attempts to find better methods to combat the issue, including ribosomally synthesized antimicrobial peptides produced by bacteria. This revolutionary solution can have both bactericidal and bacteriostatic effects on other bacteria. Generally, the strains that are closely related to the producer face its antibacterial effect. The mechanism of action of these peptides are quite diverse ranging from DNase, pore-forming, RNase, or other mechanisms. These are best defined as narrow-spectrum antimicrobial peptides and are the most promising in thwarting bacterial resistance to antibiotics.


Antimicrobial peptides or AMPs are natural antibiotics recognized for their potent antibiotic and wound healing properties. AMPs are produced by plants, animals, fungi, protozoa and bacteria. Humans have developed different strategies to cope with the harmful exposure of these pathogens; one of them being the production of AMPs.


The discovery of AMPs began in 1939 with the extraction of gramicidin from Bacillus brevis followed by the isolation of cecropins and magainins in the 1980s (Kang et al., 2017).

In most animals, AMPs are a product of innate immune responses. AMPs are oligopeptides composed of varying lengths of amino acid residues. These biomolecules are present of either cationic, hydrophobic or amphipathic nature and exhibit various biological activities against gram-positive and negative bacteria, viruses, fungi, protozoa, and even tumours.


The mechanism of antimicrobial activity is due to electrostatic interactions with the microbial cell membrane anionic phospholipids. This kind of interaction leads to perturbation or disintegration of the microbial cell membrane resulting in cell death.

The unique mechanism of AMPs that we just discussed reduces the chances of microbial resistance, unlike typical antibiotics which are usually directed towards single, mostly enzyme targets.


Due to this the development of resistance to AMPs by microbes would require them to redesign their membrane lipid composition, which is quite difficult to accomplish without causing harm to themselves. This unique property of AMPs makes them stand out as potential anti-infective molecules as antibiotic replacements for effective treatment of microbial infections.


References:

  1. Pfalzgraff, A., Brandenburg, K., & Weindl, G. (2018). Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds. Frontiers in pharmacology, 9, 281. https://doi.org/10.3389/fphar.2018.00281

  2. Kang, H. K., Kim, C., Seo, C. H., & Park, Y. (2017). The therapeutic applications of antimicrobial peptides (AMPs): a patent review. Journal of Microbiology, 55(1), 1-12.


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