An international study has shown why a fragment of a protein from the poison of a rattlesnake could be the basis for an alternative to conventional antibiotics. The research, published in the Journal of Biological Chemistry, was led by David Andreu, head of the Proteomics and Protein Chemistry Research Group at UPF, involving researchers from Australia, Portugal, Brazil and France.

The researcher Sónia Troeira Henriques, of the Institute for Molecular Bioscience (IMB) at the University of Queensland, Australia, explains that the research is significant because of the increase in the strains of drug-resistant bacteria and the few conventional antibiotics being currently developed. “This is an example of taking what nature has given us and trying to understand how it works, so we can modify it to be more potent, more stable or more drug-like, to use as an alternative to what we have in our pharmacy now”.

The research showed the peptide fragment targets the surface of the bacteria through electrostatic attractions, caused by differences in membrane properties. The peptide is positive while the bacteria is negative, allowing it to kill the bacteria by inserting and disrupting the membrane”, Dr Henriques said. “Because the cells in the body hosting the infection are neutral, they are not disrupted”, she added.

Clara Pérez-Peinado, first author of the paper and currently a PhD student with David Andreu’s team at the Department of Experimental and Health Sciences (CEXS), had previously discovered that the fragment retained the antimicrobial potency of the full peptide, but was harmless to non-bacterial cells, and, furthermore, highly resistant to serum proteases, an uncommon property in peptides showing great promise with a view to pharmacological application.

The research is being carried out on strains of bacteria including some that cause serious infections in hospitals. It is usually very difficult to attack these bacteria because they have an extra membrane and are often camouflaged by a protective capsule.

“The results suggest a promising role for this fragment of crotalidicin, and are continuing to confirm that peptides, when appropriately redesigned, are effective antibiotics against resistant bacteria”, points out David Andreu.

The researchers are involved in a research and innovation staff exchange programme funded by the European Commission within the Horizon 2020 framework. Thanks to this programme that allows mobility and knowledge transfer between institutions, Clara Pérez-Peinado has enjoyed a long stay at the Institute of Molecular Medicine, at the University of Lisbon, and David Andrew and Sira Defaus, from the same laboratory, stays of six months at the IMB in Brisbane, Australia.

Reference article:

Pérez-Peinado C, Almeida S, Domingues M, Benfield A, Freire JM, Radis-Baptista G, Gaspar D, M Castanho, Craik D, Henriques S, Veiga A, Andreu D. Mechanism of bacterial membrane permeabilization of crotalicidin (Ctn) and its fragment Ctn[15-34], antimicrobial peptides from rattlesnake venom. Journal of Biological Chemistry, February 2018.