When infected wounds – often arising from surgery, diabetes or everyday injuries – fail to heal, they can become chronic infections that linger for weeks and become difficult to treat.
This places a heavy burden on patients and healthcare systems, with the risk of serious complications such as amputations.
A new study has now uncovered a key mechanism that explains why these infections are so difficult to treat and why they frequently become more complex over time.
Led by researchers from the Singapore‑MIT Alliance for Research and Technology’s (SMART) Antimicrobial Resistance (AMR) interdisciplinary research group, the multinational team discovered how a common bacterium found in wounds, Enterococcus faecalis, releases large amounts of lactic acid during infection, acidifying the surrounding tissue environment.
This acidity suppresses the activation of macrophages – immune cells that normally help to clear infections – and interferes with several important internal processes that help the cell recognise and respond to infection.
As a result, the mechanisms that cells rely on to send out “danger” signals are suppressed, effectively “switching off” the body’s line of defence.
This weakened immune system allows E. faecalis to persist far longer than it should and creates a weakened environment where other bacteria, such as Escherichia coli, can flourish.
This results in persistent, polymicrobial wound infections, such as diabetic foot ulcers and post‑surgical complications, where multiple bacterial species make treatment more challenging.
In their paper published in the journal Cell Host & Microbe, the researchers showed through mouse wound models that strains of E. faecalis unable to produce lactic acid were cleared much faster, with the wounds showing stronger immune activity.
In models infected with both E. faecalis and E. coli, the weakened immune response caused by lactic acid also allowed E. coli to grow better.
“Chronic wound infections often fail not because antibiotics are powerless, but because the immune system has effectively been ‘switched off’ at the infection site,” says study first author and SMART AMR research scientist Dr Ronni da Silva.
“We found that E. faecalis floods the wound with lactic acid, lowering pH and muting the ‑κB alarm inside macrophages – the very cells that should be calling for help.
“By pinpointing how acidity rewires immune signalling, we now have clear targets to reactivate the immune response.”
