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European Antibiotics Awareness Day (EAAD) occurs every year on 18 November. Established in 2008 by the European Centre for Disease Prevention and Control, the day aims to raise awareness about the global and escalating issue that is antimicrobial resistance (AMR). Don Whitley Scientific acknowledges this day by exploring whether antimicrobial peptides may be a solution.
The requirement for novel antimicrobial agents is becoming ever more urgent as AMR levels increase around the world. Due to the unsatisfactory outcomes of traditional antimicrobial treatments, alternative therapies are becoming more well-recognised, including antimicrobial peptides (AMPs) [1]. AMPs are pre-existing, naturally occurring molecules that have been universally present in the gene pool of bacteria for a very long time and are the first line of defence for a range of organisms [1]. They are proving favourable as an alternative treatment as they have broad spectrum activity against both Gram-negative and positive bacteria as well as fungi; in addition, their low immunogenicity and mutagenicity makes them a positive candidate for targeting multi-drug-resistant pathogens [1]. Research has shown that the genomics of AMPs are vital for understanding their efficacy and ability to have maximum antimicrobial activity, for example, activity is dependent on the content of lipophilic groups as opposed to the amino sequence [1]. Metagenomics has therefore become a key area of investigation.
Laverty et al. determined that the lipopeptide C12-OOWW-NH2 was one of the most potent antimicrobial agents, but as it is a synthetic compound, there is an arguable preference for more naturally occurring peptides [2]. As a result, Megaw et al. had their study published this year, which aimed to identify naturally occurring peptides with the same structural properties as C12-OOWW-NH2, but also with the same potency [1]. They selected several peptides for synthesis and then screened them against a range of bacterial strains including Pseudomonas aeruginosa, Bacillus cereus and Clostridium perfringens [1]. All strains were incubated at 37°C aerobically, except for C. perfringens which was grown in a Whitley Anaerobic Workstation with an atmosphere of 80% N2, 10% CO2, and 10% H2 [1]. Antimicrobial activity was determined using zones of inhibition and minimal inhibitory concentrations using the broth microdilution method [1]. In addition, they investigated how modifications to their peptides affected antimicrobial activity and found that extending the peptide and including a C-terminal strengthened activity [1]. A promising candidate named PB2-10aa-NH2 was identified and with modifications, there was improved thermostability and solubility as well as a synergistic effect with ethanol [1]. This is encouraging as imbedding the agent into the phospholipid bilayer has a strong correlation with antimicrobial activity [1]. Ultimately, if a natural AMP alternative to the potent synthetic AMP is available then this would be preferable, so research of this kind is extremely vital.
Favourable results in AMR research, such as those gained from metagenomic studies, provide hope that we can reduce AMR and potentially one day solve the problem once and for all.
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References:
- Megaw J, Skvortsov T, Gori G, Dabai AI, Gilmore BF, Allen CCR. A novel bioinformatic method for the identification of antimicrobial peptides in metagenomes. Journal of Applied Microbiology. 2024 Feb 21;135(3):lxae207.
- Laverty G, McLaughlin M, Shaw C, Gorman SP, Gilmore BF. Antimicrobial Activity of Short, Synthetic Cationic Lipopeptides. Chemical Biology & Drug Design. 2010 Mar 30;75(6):563–9.
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