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New molecule created in the fight against bacteria showing Anti-Microbial Resistance
November 17, 2023

Researchers at Maynooth University working as part of an international team have created a new molecule that could help in the fight against drug-resistant bacteria, writes Dr Robert Elmes of the Department of Chemistry.

Pictured from left to right: Professor Kevin Kavanagh, Department of Biology; Conor Geraghty, Department of Chemistry; Magdalena Piatek, Department of Biology; Luke Brennan, Department of Chemistry; Conor Wynne, Department of Chemistry; Dr Robert Elmes, Department of Chemistry

AMR occurs when bacteria, viruses, fungi and parasites change over time and no longer respond to medicines, making infections harder to treat and increasing the risk of disease, severe illness and death. The development of new ways to kill bacteria is an urgent scientific need, as most conventional antibiotics will no longer be effective in 2050 due to the rising levels of AMR.

In work supported by the SSPC, SFI’s Pharmaceutical Research Centre and the Irish Research Council, researchers from Maynooth University, as part of an international team, have created a new molecule that could prove useful in the fight against bacteria showing Anti-Microbial Resistance (AMR). The development of new ways to kill bacteria is an urgent scientific need, as most conventional antibiotics will no longer be effective in 2050 due to the rising levels of AMR.

The breakthrough harnesses the principles of supramolecular chemistry; a niche scientific area that explores interactions between molecules.

Lead researcher Luke Brennan said, “We are discovering new molecules and looking at how they bind to anions; negatively charged chemicals that are extremely important in the context of the biochemistry of life. We are laying the fundamental foundations that could prove useful in combatting various diseases from Cancer to Cystic Fibrosis”.

The work is based on the use of synthetic ion transporters and is the first time that researchers have demonstrated that an influx of salt (sodium and chloride ions) into the bacteria can cause a series of biochemical events that lead to bacterial cell death – even in strains that are resistant to currently available antibiotics such as methicillin-resistant Staphylococcus aureus (MRSA).

The new research is described this week in the prestigious journal Chem (Cell Press) where it has been chosen as the cover article, to coincide with World AMR Awareness Week (WAAW, 18th – 24th November); a global campaign to raise awareness and understanding of AMR in the hope of reducing the emergence and spread of drug-resistant infections. More than 1.2 million people – and potentially millions more – died in 2019 as a direct result of antibiotic-resistant bacterial infections, according to the most comprehensive estimate to date of the global impact of AMR. This research may pave the way for new approaches to tackle this problem that kills more people annually than HIV/AIDS or malaria.

Study co-author Dr Rob Elmes of Maynooth University’s Kathleen Lonsdale Institute for Human Health Research, says: “This work shows how using our approach, a sort of ‘trojan horse’ that causes an influx of salt into cells, we can effectively kill resistant bacteria in a way that counteracts known methods of bacterial resistance”.

Bacteria work hard to maintain a stable concentration of ions inside their cell membranes, and when  this delicate balance is disrupted it wreaks havoc on normal cell function and the cells cannot survive.

Elmes continued “These synthetic molecules bind to chloride ions and wrap it up in a ‘fatty blanket’ that allows it to easily dissolve in the bacteria’s membranes, bringing the ions along for the ride and disrupting the normal ionic balance. The work is a great example of foundation knowledge in chemistry fundamentals impacting on unmet needs in human health research”.

Most importantly, the study found that while these molecules are efficient at killing bacteria, their toxicity to healthy human cells was very low.

Professor Kevin Kavanagh, a microbiologist on the Department of Biology at Maynooth commented “The rising incidence of infections by drug resistant bacteria is a major concern. This work is an example of chemists and biologists working together to pioneer the development of new antimicrobial agents with significant future potential”.

Such results pave the way for the potential development of anion transporters as a viable alternative to currently available anti-biotics, something urgently required as the problem of AMR continues to rise.

On the cover: The image conveys the ability of the synthetic molecules (squindoles) reported in this issue by Gale, Kavanagh, Elmes, and colleagues (page 3138) to efficiently transport chloride ions through lipid membranes and thereby disrupt ion homeostasis and result in potent anti-microbial activity. Copyright Ella Maru.

Link: https://www.sciencedirect.com/science/article/pii/S2451929423003650

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