A multi-disciplinary project driven by EMBL Australia researchers at Monash University and Harvard University has found a way to make antibiotics more effective against antibiotic-resistant bacteria - also known as ‘superbugs.
Antimicrobial resistance to superbugs has been evolving and is one of the top 10 global public health threats facing humanity, according to the World Health Organization.
This new research will provide a pathway to increasing the effectiveness of antibiotics, without clinicians having to resort to risky strategies of giving patients higher doses or relying on the discovery of new types of antibiotics.
During a bacterial infection, the body uses molecules called chemoattractants to recruit neutrophils to the site of the infection. Neutrophils are immune cells with the ability to encapsulate and kill dangerous bacteria, critical to the immune response. Researchers attached a chemoattractant to an antibiotic, enabling them to enhance the recruitment of immune cells and improve their killing ability.
The findings have now been published in Nature Communications.
“When looking at how our immune system can fight bacteria there are two important aspects we look at. The first is our ability to entrap bacterial cells and kill them. The second is the signals – the chemoattractants – calling for more neutrophils, white blood cells which lead the immune system's response to resolve infection,” said Dr Jennifer Payne, the lead researcher from EMBL Australia and the Monash Biomedicine Discovery Institute.
The researchers linked a chemoattractant known as formyl peptide to vancomycin, a commonly used antibiotic that binds to the surface of the bacteria, and performed their studies on golden staph infections, one of the more problematic antibiotic-resistant bacteria.
“We’ve been working on using dual-function antibiotic-chemoattractant ‘hybrids’, which improve the recruitment of neutrophils and increase the engulfing and killing of the bacteria,” said Dr Payne.
“By stimulating our powerful immune system in this way with the immunotherapeutic antibiotic, we’ve shown in mouse models that the treatment is 2-fold more effective than just using the antibiotic alone at one-fifth lower dose,” said Associate Professor Max Cryle, an EMBL Australia Group Leader at the Monash Biomedicine Discovery Institute.
“This very promising new avenue of research is bringing a lot of potential benefits to the ever-increasing threat of drug-resistant superbugs,” said Associate Professor Cryle.
Instrumental to the project was funding from VESKI and Melbourne sister city foundation that took Dr Payne across the world to Boston to learn and carry out microfluidic research learning and collaborating with Associate Professor Daniel Irima, and Dr Felix Ellett, Harvard experts in this field.
“Microfluidics was ground-breaking for this research, as it allowed us to generate an infection-on-a-chip to monitor the recruitment of human immune cells, and observe in real-time how our immunotherapeutic enhances their ability to kill MRSA. Just like what would happen in our body” said Dr Payne,
Partners are being sought to continue this research into clinical trials with the potential of developing a preventative antibiotic strategy in the intensive care environment to protect our most vulnerable.
The work has resulted in a patent covering the immunotherapeutic, with the IP owned by Monash University.
Watch our animation, Using immunotherapeutics to tackle the threat of superbugs, which explains the threat of superbugs and what our talented researchers are doing to address the problem.
Read the full paper in Nature Communications titled: Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus
DOI : 10.1038/s41467-021-26244-5
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About EMBL Australia
EMBL Australia is a life science network that supports ambitious research projects and provides access to infrastructure and training to early-career Australian scientists.
Australia is an associate member of the European Molecular Biology Laboratory (EMBL), Europe’s flagship life sciences institution.
The associate membership gives Australia the opportunity to internationalise our life sciences research, introduce the world’s best young researchers to new networks and tools here in Australia, and develop highly competitive research teams networked across the nation and with Europe and Asia.
Supported by the National Research Infrastructure for Australia (NCRIS) program, an Australian Government initiative, EMBL Australia is at the cutting edge of life sciences research in Australia.
About the Monash Biomedicine Discovery Institute at Monash University
Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally renowned research teams. Spanning six discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection and Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.
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Subject of Research
Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus
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