New technique gives new weapon to antibiotics in the fight against superbugs

Superbugs have long been fighting back against their slayers – antibiotics – but new research has uncovered a way for antibiotics to launch their own fightback against the superbugs.

Drug-resistant bacteria are listed by the World Health Organization as one of the 10 most pressing public health threats due to their potential to render antibiotics ineffective. A multi-disciplinary project from EMBL Australia researchers at Monash University and Harvard University, however, has found a way to make antibiotics more effective against bacterial infection.

The research, published in Nature Communications, has the potential to increase the efficacy of antibiotics without clinicians having to resort to the risky strategy of increasing doses for patients, 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. Researchers attached a chemoattractant to an antibiotic, enabling them to increase the recruitment of immune cells and improve their ability to kill the bacteria.

“When looking at how our immune system can fight bacteria, there are two important aspects we look at,” says Dr Jennifer Payne, the lead researcher from EMBL Australia and the Monash Biomedicine Discovery Institute. “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.

Read more: Down with the (antibiotic) resistance!

The researchers linked a chemoattractant known as formyl peptide to vancomycin, a commonly used antibiotic that binds to the surface of the bacteria. They performed the studies on one of the more problematic and powerful antibiotic-resistant bacteria: Staphylococcus aureus, or golden staph.

Bacteria and neutrophils under microscope
The lab on a chip: bacteria (stained red), being targeted by neutrophils (stained blue). Credit: Dr Jennifer Payne

“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,” says Payne.

As part of the research, Payne collaborated with microfluid experts from Harvard University, USA. “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” says Payne.

Associate Professor Max Cryle of the Monash Biomedicine Discovery Institute and EMBL Australia Group Leader predicts that the research will have many potential benefits in the fight against drug-resistant superbugs.

“By stimulating our powerful immune system in this way with the immunotherapeutic antibiotic, we’ve shown in mouse models that the treatment is twofold more effective than just using the antibiotic alone at one-fifth lower dose,” he says.

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