Stressing the Bugs: New Treatment Targets for Multidrug Resistant Bacteria

By Prashant Kumar, PhD Candidate in Kizhakkedathu Lab, CBR

An abscess is a collection of pus in the skin, which can eventually cause skin lesions. Many different bacteria can cause abscesses but methicillin resistant S. aureus (MRSA) has become a major contributor. Conventional antibiotics are not effective against abscesses and the overuse of antibiotics has already resulted in the emergence of multidrug resistant bacteria. Regulatory mechanisms that govern abscess pathology are currently not well understood.

In a study published in EBioMedicine, Sarah Mansour and her colleagues in the Hancock lab at the CBR discovered that resistant abscesses can be treated by targeting the bacterial response to stress.

“Bacteria produce a stress response in order to thrive in the hostile skin environment. This response is also important for forming biofilms, which are slimy clusters of bacteria that become significantly more resistant to traditional antibiotic treatments.”- explained Sarah Mansour, a PhD candidate.

The Hancock lab also demonstrated that a small synthetic peptide, called DJK-5, can inhibit the formation of MRSA biofilms. Due to the mechanistic overlap, the authors decided to directly inject the peptide into the abscesses formed by MRSA and saw that DJK-5 drastically decreased the skin damage in mice.

They showed that DJK-5 peptide acts by suppressing the production of a major S. aureus toxin, which is activated under stress conditions and promotes bacterial survival. The peptide was effective against both Gram positive and Gram negative bacteria.

“The major discovery of this publication is that the bacterial stress response is a critical determinant in abscess pathology.” – Sarah commented.

Targeting this pathway to reduce the severity of abscess infections is an approach that is entirely different from every known antibiotic. It can now serve as a novel strategy for combating multidrug resistant bacteria.

The next step in the research is to determine whether this peptide can be used in combination with conventional antibiotics. Synergistic formulas can help to substantially reduce the dose of antibiotics required to eradicate infections, potentially decreasing antibiotic resistance.

This publication was also covered by Metro News and UBC News.