Chronic wounds are often dismissed as slow-healing injuries, but for millions of people — especially those recovering from surgery or living with diabetes — they can become long, stubborn infections that refuse to close. Unlike ordinary cuts or wounds that heal within days, these can linger for weeks or even months, sometimes developing into serious conditions such as diabetic foot ulcers (DFU).
A new international study has identified a key reason why some wounds fail to heal. It points to a common bacterium that can effectively “switch off” the body’s immune response, allowing infections to linger and recovery to stall.
Published in the journal Cell Host & Microbe, the research shows that Enterococcus faecalis—frequently found in chronic wounds and hospital environments—uses a biochemical mechanism to suppress the body’s natural defences.
How bacteria weaken the immune system
The study, led by researchers from the Researchers from the Singapore MIT Alliance for Research and Technology’s (SMART) Antimicrobial Resistance (AMR) together with collaborators from SCELSE, Nanyang Technological University (Singapore), Massachusetts Institute of Technology (MIT) and the University of Geneva found that E faecalis produces high levels of lactic acid in wounds. This increases acidity, lowering the pH and disrupts immune function.
At the centre of the process are macrophages, immune cells that act as first responders to infection. Normally, these cells activate a signalling pathway known as NF-κB, which triggers inflammation and helps eliminate harmful microbes.
However, the study found that lactic acid interferes with this pathway. It enters immune cells through a transporter (MCT-1) and binds to a receptor (GPR81), effectively shutting down the NF-κB signal. As a result, the immune system fails to mount a strong defence.
A gateway for more infections
The effects are not limited to a single bacterium.
By weakening immune responses, E faecalis creates conditions in which other pathogens — such as Escherichia coli — can also thrive. This leads to polymicrobial infections, where multiple microbes coexist, making treatment far more complex.
Laboratory experiments using wound models showed that when the bacterium was unable to produce lactic acid, immune responses improved and wounds healed faster. In contrast, higher acidity prolonged infection and encouraged bacterial growth.
The findings suggest that lactic acid-driven immune suppression may be a key factor behind persistent infections.
What this could mean for treatment
Rather than relying solely on antibiotics, the research points towards new approaches that support the body’s own immune response. These could include reducing wound acidity or blocking the pathways used by lactic acid to suppress immune cells.
Researchers say they now plan to test their findings in human wound samples and move towards clinical trials. If successful, the approach could pave the way for more effective treatments for chronic wounds while reducing dependence on antibiotics.
“This discovery deepens our understanding of how bacteria evade immune defences and opens new avenues for treatments that target these mechanisms,” said professor Kimberly Kline, principal investigator at SMART AMR and corresponding author of the study. “By showing how the immune response is suppressed, it could improve infection management and recovery, especially for patients with chronic wounds or weakened immunity.”
Why it matters for India
The findings offer fresh hope for managing persistent wound infections and accelerating healing—potentially improving quality of life for millions of patients.
Chronic wounds already place a heavy burden on healthcare systems worldwide, with a high risk of complications, including amputations. The challenge is particularly acute in low- and middle-income countries, where access to timely care and follow-up treatment can be limited.
The implications are especially significant for India, which has a large and growing population of people living with diabetes. With an estimated 90 million adults living with diabetes as of 2024, second only to China, even modest improvements in treatment could have a significant public health impact.
DFUs alone affect around 6.2 per cent of people with diabetes in India, underscoring the scale of the challenge and the potential value of new, more effective therapies.
