Targeting bacterial communication may offer antibiotic-free wound therapy

Researchers at University of California San Diego School of Medicine have discovered a previously unrecognized mechanism by which Staphylococcus aureus - one of the most common causes of skin and soft tissue infections worldwide - delays wound healing. The new study reveals that quorum sensing - a process in which bacteria communicate and coordinate behavior with one another - is a key driver of delayed healing in wounds infected by S. aureus. The findings suggest that by using drugs to interfere with quorum sensing, it could be possible to enhance wound healing without relying on antibiotics, reducing the risk of resistance and improving healing outcomes for patients.

Despite significant advances in wound care, infections by S. aureus, particularly methicillin-resistant strains (MRSA), remain a leading cause of delayed wound healing and poor patient outcomes around the world. MRSA infection is particularly common in hospital settings, accounting for a significant portion of surgical site infections, bloodstream infections and pneumonia in hospitalized patients.

The researchers found:

• In both mouse and human models of wound healing, infection with S. aureus activated the bacterium's accessory gene regulator (agr) quorum-sensing system, a molecular "switch" that controls bacterial communication and virulence.
• Activating the agr system led to a dramatic suppression of key metabolic genes in keratinocytes, cells that help rebuild the skin barrier during wound healing.
• Disruption of the agr system in S. aureus restored normal wound healing and keratinocyte function, even when the bacteria were present at high levels.
• In contrast, exposure to harmless bacteria such as Staphylococcus hominis did not impair healing and even promoted beneficial metabolic activity in skin cells.

These findings have significant implications for the treatment of chronic wounds and hospital-acquired infections. By targeting the agr system, it may be possible to disarm S. aureus without relying on antibiotics, reducing the risk of antibiotic resistance and improving healing outcomes for patients. The study also highlights the importance of the wound microbiome and suggests that therapies which preserve or restore healthy skin bacteria could enhance recovery.

While further research and clinical trials are needed to translate these insights into specific therapies, the results open the door to innovative approaches for managing wound infections, potentially transforming care for patients with chronic and hard-to-heal wounds.

The study, published in The Journal of Clinical Investigation, was led by Michelle D. Bagood, Ph.D., a postdoctoral researcher, and Richard L. Gallo, M.D., Ph.D., professor and chair of the Department of Dermatology at UC San Diego School of Medicine. The work was funded, in part, by grants from the National Institutes of Health. Gallo is a cofounder, scientific advisor, consultant, and equity holder of MatriSys Bioscience.