Dr. Marta Martins

Summary

The worldwide occurrence of antimicrobial resistance and the lack of new antibiotics is jeopardising our ability to treat infections. This triggered the search for novel molecules as well as for the repurposing of existing drugs. One of these compounds, Thioridazine, with activity reported against Mycobacterium tuberculosis will be studied to elucidate its mechanism of action using Salmonella as a model of infection, focusing on its effects on the infected host cells.

Funding Agency

Welcome Trust

Programme

ISSF funding

Project Type

Research

Summary

In this project we used a computational data-mining and feature based approach to unravel the abundance of unexplored peptides from nature and to identify potent, novel antimicrobial peptides (AMPs) from phyto-proteins. We explored Pisum sativum hydrolysed (PSH) protein and evaluated its potential as a bio-preservative. As the "clean label" revolution takes hold, paired with increased consumer demand for natural products, alternative preserving solutions are needed to maintain food safety and limit spoilage. PSH offers an attractive plant-based solution, capable of reducing disease causing pathogens while being economically viable, and environmentally friendly. Expanding on the potential of the PSH, we identified NuriPep 1653, an individual peptide component of the hydrolysate with remarkable antimicrobial activity. AMPs are an integral part of every species contributing to host defence and have been lauded as contenders in combatting the antibiotic crisis. Despite immense scientific efforts to bring antibiotic alternatives to the market, very few have been approved for market sale as they have yet to surpass the activity of traditional therapies. Paired with the reluctance from the pharmaceutical industry to financially support antimicrobial research, this means that the need for novel antimicrobial compounds has never been greater. We have explored the therapeutic potential of NuriPep 1653 against clinically relevant pathogens and highlighted its appeal for the pharmaceutical sector given its limited propensity for inducing resistance, rapid kill kinetics, non-toxic nature, ability to reverse resistance and synergise with conventional antibiotic therapies. Moreover, NuriPep 1653 reduced the activation of pathways and cytokines associated with pro-inflammatory response indicating its abilities to modulate the host immune response. This vastly expands the therapeutic potential of the peptide. Overall, we were able to use a novel discovery approach to identify AMPs encrypted within phyto-proteins. Through PSH and NuriPep 1653, we hope to expand on the current knowledge related to protein hydrolysates and AMPs and inch closer to providing novel antimicrobial solutions across the food and pharmaceutical industries.

Funding Agency

Irish Research Council (IRC)

Programme

Employment based programme

Project Type

Research