A New Tool for Fighting Serious Bacterial Skin Infections

In a recent study in mice, researchers used a synthetic peptide to disrupt the bacterial stress response that causes abscess formation in skin infections with drug-resistant bacteria. Sarah C. Mansour, from the University of British Columbia, Vancouver, Canada, and colleagues published the results of their study in EBioMedicine.

“[W]e demonstrated that the stringent stress response employed by bacteria to cope and adapt to environmental stressors was essential for the formation of lesions, but not bacterial growth, in a methicillin resistant Staphylococcus aureus (MRSA) cutaneous abscess mouse model,” the authors write.

According to Mansour and colleagues, skin abscesses account for more than 3 million visits to emergency departments each year. In severe cases, abscesses may need to be surgically drained in addition to antibiotic treatment. MRSA infections are also now emerging as an important cause of skin and soft-tissue infections, including skin abscesses.

Although trimethoprim-sulfamethoxazole, clindamycin, and tetracyclines are among the antibiotics frequently used to treat abscesses associated with MRSA infection, conditions inside the abscess (such as acidic pH, debris, and high bacterial counts) often contribute to treatment failure because they prevent antibiotic penetration into the abscess. Combined with antibiotic overuse in recent decades, this has subsequently resulted in bacterial strains that are resistant to most antibiotics.

The researchers hypothesized that abscesses arise due to a distinct stress-triggered growth state in bacteria that leaves them not only able to cause pathology, but also become resistant to treatment. They considered involvement of the stringent stress response that bacteria use in reaction to a reduced supply of amino acids, fatty acids, carbon-source, oxygen, or iron; bacteria may also use this response under conditions of heat shock, antimicrobial challenge, and/or other environmental stressors.

The researchers used DJK-5 to show how the stringent stress response in bacteria leads to abscess formation in mice. DJK-5 is a cationic peptide that causes rapid breakdown of the stringent response mediator, guanosine tetraphosphate (ppGpp).

“[W]e showed that stringent stress adaption is a critical determinant of S[taphylococcus] aureus cutaneous abscess lesion formation,” the authors write. They found that bacteria in abscesses were in a stress-triggered growth state. Using DJK-5, they were able to interfere with the bacterial stress response and suppress abscess formation in mice. “The therapeutic application of this peptide strongly inhibited lesion formation in mice infected with Gram-positive MRSA and Gram-negative Pseudomonas aeruginosa,” the authors write.

In a news release, the study’s senior author, Bob Hancock, explained that after DJK-5 is taken up into the bacterium, it binds to a signaling molecule that is involved in the stress response. This leads to breakdown of the signaling molecule by bacterial enzymes, “essentially making the micro-organism forget that it’s under stress.”

Due to the fact that its mechanism of action is different from those of antibiotics, DJK-5 peptide therefore represents a new approach to treating bacterial infections.

“[W]e have uncovered mechanisms driving bacterial abscess lesion formation and provide a therapeutic approach to minimize the severity of skin infections by both Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa,” the authors conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.