A CARB-X funding grant will support UNSW researchers exploring new ways to combat antibiotic-resistant infections.
UNSW Sydney researchers have been awarded more than $1.2 million in funding to advance the development of a potential new class of antibiotics to tackle drug-resistant bacterial infections.
Dr Bryson Hawkins from UNSW Medicine & Health has received $US852,972 ($1.246 million) from Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), a global non-profit partnership dedicated to supporting early-stage antibacterial research and development. UNSW will also contribute $US150,702 ($220,166) in funding to the research project.
Dr Hawkins and his team, in partnership with biotechnology company Donum Therapeutics, will focus on developing synthetic versions of darobactin, a naturally occurring peptide antibiotic – found in bacteria associated with roundworms – which shows promise for treating some multi-drug-resistant bacteria.
“This support will enable UNSW and Donum Therapeutics to advance the discovery of a new class of antibiotics – reimagining nature’s own molecules through chemistry in a bid to treat drug-resistant infections that current therapies can no longer defeat,” said Dr Hawkins.
Addressing a growing global health challenge
Antimicrobial resistance (AMR) occurs when bacteria evolve to resist medicines designed to kill them, making infections increasingly difficult to treat. It is considered one of the most urgent threats to modern medicine and is predicted to contribute to an estimated 39 million deaths over the 25 years to 2050.
Researchers are particularly concerned about Gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, which are responsible for a range of serious infections.
A major challenge is cross-resistance, which occurs when a bacterium adapts to resist one antibiotic and, as a result, becomes resistant to other similar antibiotics, limiting treatment options.
“Many newer antibiotics are based on existing medicines, and bacteria are increasingly finding ways to resist them. That’s why we urgently need new approaches to tackle drug-resistant infections,” Dr Hawkins said.
Building on a promising discovery
Darobactin was first identified in 2019 during efforts to discover new antibiotics from natural sources. It is found in bacteria associated with insect-hunting nematodes, or roundworms, where it helps protect the worms and their bacterial partners from competing microbes.
Unlike existing antibiotics, darobactin attacks bacteria by targeting BamA, a protein essential for building and maintaining the protective outer membrane of Gram-negative bacteria. This new target may allow darobactin to remain effective against some multidrug-resistant bacteria.
“What makes darobactin exciting is that it targets bacteria in a completely different way from existing antibiotics,” Dr Hawkins said. “That gives us an opportunity to explore a new path for treating infections that are already resistant to current medicines.”
While naturally occurring compounds can provide valuable starting points for drug discovery, significant development is often required before they become viable medicines.
Turning a natural antibiotic into a medicine
The team will focus on redesigning darobactin to create synthetic versions that may be more potent and better suited to future clinical development.
“We have a promising starting point for a new antibiotic, but now we want to improve its potency and ensure it has the properties needed for further development as a safe and effective medicine. This funding will allow us to design, test and refine new versions of darobactin, ultimately identifying the strongest candidates to take forward in the antibiotic development pipeline,” Dr Hawkins said.
CARB-X Chief of Research and Development Richard Alm said new antibiotic classes were key to overcoming the challenge of cross-resistance.
“When a single genetic change can render an entire class of medications ineffective, doctors can quickly run out of options to treat serious infections, and patient outcomes suffer. New antibiotic classes, like darobactin, can introduce new ways of targeting bacteria and may avoid cross-resistance with existing antibiotics,” he said.
“This award reflects our commitment to supporting innovative approaches aimed at treating some of the most dangerous bacterial infections facing patients worldwide.”
Professor Cheryl Jones, Dean of UNSW Medicine & Health, said funding early-stage antibiotic research was critical to building the pipeline of new treatments needed to address the growing threat of antimicrobial resistance.
“This investment will help our researchers move promising discoveries closer to the clinic, where they have the potential to improve outcomes for patients facing infections that are becoming increasingly difficult to treat.”
