Superbugs are strains of bacteria, viruses, parasites, and fungi that are resistant to most of the antibiotics and other medications commonly used to treat the infections they cause. Antimicrobial resistance can be slowed, but not stopped. Over time, germs such as bacteria, viruses, parasites, and fungi adapt to the drugs that are designed to kill them and change to ensure their survival. A new study demonstrates a novel way of making antibiotics more effective against antibiotic-resistant bacteria.
The study, “Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus,” is published in the journal Nature Communications and led by researchers at EMBL Australia, Monash University, and Harvard University.
“The pathogen Staphylococcus aureus can readily develop antibiotic resistance and evade the human immune system, which is associated with reduced levels of neutrophil recruitment,” the researchers wrote. “Here, we present a class of antibacterial peptides with potential to act both as antibiotics and as neutrophil chemoattractants.”
“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,” explained Jennifer Payne, PhD, the lead researcher from EMBL Australia and the Monash Biomedicine Discovery Institute.
The researchers linked formyl peptide to vancomycin, and performed their studies on golden staph infections.
“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 Payne.
“By stimulating our powerful immune system in this way with the immunotherapeutic antibiotic, we’ve shown in mouse models that the treatment is two-fold more effective than just using the antibiotic alone at one-fifth lower dose,” said associate professor Max Cryle, PhD, 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,” added Cryle.
“We use a combination of in vitro assays, cellular assays, infection-on-a-chip, and in vivo mouse models to show that the compounds improve the recruitment, engulfment, and killing of S. aureus by neutrophils,” the researchers wrote. “Furthermore, optimizing the formyl peptide sequence can enhance neutrophil activity through differential activation of formyl peptide receptors. Thus, we propose antibiotic-chemoattractants as an alternate approach for antibiotic development.”
“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 Payne.
The new findings pave a way for improving the effectiveness of antibiotics without clinicians having to rely on higher doses or the discovery of new types of antibiotics.
