Scientists have found a way to boost the antibacterial activity of an antimicrobial peptide originating from a spider, according to a recent publication in the journal ACS Chemical Biology.
With increasing rates of antimicrobial resistance a global concern, scientists are attempting to find alternatives to the traditional antibiotic drugs which we have relied on for so many years. One of the most attractive new treatments are antimicrobial peptides (AMPs), naturally occurring molecules in all plants and animals which are associated with several benefits. Resistance to their action is much less common, owing to their broader system of targeting – for example, AMPs typically kill bacteria by disruption of the cell membrane, whereas antibiotics often target specific cellular processes, against which a resistance –granting mutation is easier to develop. AMPs also are less likely to exhibit dangerous effects towards human cells, as they have a preference for the structure of bacterial cells.
The AMP gomesin, derived from the Brazilian spider Acanthroscurria gomesiana, has shown efficacy against gram-negative bacteria, and also against melanoma cells. However, a subsequent study found that when the structure of the AMP was changed from linear to cyclic, gomesin retained its activity but became much more stable.
Now, researchers from the University of Queensland Institute for Molecular Bioscience, Brisbane, attempted to modify this cyclic structure further, to improve gomesin’s activity while still keeping its stability. They also wanted to answer the question of why gomesin showed particular activity against melanoma cancer cells.
The team created several modified versions of cyclic gomesin, and tested these modified AMPs against a range of bacteria, including the gram-positive Staphylococcus aureus and the gram-negative Escherichia coli.
It was found that the modified form with a higher overall charge than the original AMP, [G1k,K8R]cGm, had the best antibacterial activity against all organisms tested. The modified peptides also showed high stability in serum, and low toxicity towards red blood cells.
The researchers were then able to show that the modified peptides retained their efficacy against various cancer cell types, including chronic myeloid leukaemia (CML) cells – however, their activity varied depending on the cell type. The team concluded that this was because of the difference in composition of the cell membranes. For example, CML cells lack heparan sulfate groups on their cell surface, which increases their overall charge, as opposed to other cell types which do have these groups. This difference in charge appeared to affect the activity of the modified AMPs. It’s likely that the modified gomesin structures kill the cancer cells in the same way as bacterial cells.