Bacteria Suppress Immunity in Stubborn Wound Infections: New Research Reveals How
Chronic wound infections, stubbornly resistant to treatment, may stem from a surprising tactic employed by Enterococcus faecalis (E. Faecalis), a common bacterium. New research illuminates how this resilient microbe doesn’t just invade tissue, but actively suppresses the body’s immune defenses by flooding the wound with lactic acid. This discovery, published in Cell Host &. Microbe, offers a potential explanation for why some wounds, like diabetic foot ulcers and post-surgical infections, struggle to heal and why multi-species infections are so difficult to eradicate.
Researchers from the Singapore-MIT Alliance for Research & Technology’s (SMART) Antimicrobial Resistance (AMR) interdisciplinary research group, working with collaborators from SCELSE at Nanyang Technological University (NTU Singapore), Massachusetts Institute of Technology (MIT) and the University of Geneva (UNIGE), demonstrated this immune suppression in a mouse wound model. The study revealed that E. Faecalis releases significant amounts of lactic acid, acidifying the tissue environment and effectively silencing the immune response. This isn’t simply a matter of the bacteria surviving; it’s actively preventing the body from fighting back.
How Lactic Acid Dampens the Immune Response
Macrophages, key immune cells responsible for clearing infections, are particularly vulnerable to the effects of lactic acid. The researchers found that E. Faecalis utilizes a two-step mechanism. First, lactic acid enters macrophages via a lactate transporter called MCT-1. Second, it binds to a lactate-sensing receptor, GPR81, on the cell surface. This dual action disrupts crucial internal processes within the macrophage, preventing it from recognizing and responding to the infection. Specifically, the lactic acid interferes with the activation of NF-κB, a key immune alarm signal.
This suppression isn’t theoretical. When researchers used strains of E. Faecalis unable to produce lactic acid in the mouse model, the wounds healed more quickly and exhibited stronger immune activity. In wounds infected with both E. Faecalis and Escherichia coli (E. Coli), the lactic acid-induced immune weakening allowed the E. Coli to flourish, highlighting how E. Faecalis can pave the way for more complex, polymicrobial infections. As reported by The Microbiologist, this explains why wound infections often involve multiple bacterial species and become increasingly challenging to treat over time.
Beyond E. Faecalis: Implications for Chronic Wounds
E. Faecalis is frequently found in chronic wounds, making this discovery particularly relevant. These persistent wounds place a substantial burden on both patients and healthcare systems, sometimes leading to severe complications like amputations. The study suggests that chronic wound infections often fail to respond to antibiotics not because the drugs are ineffective, but because the immune system has been effectively neutralized at the site of infection.
“We found that E. Faecalis floods the wound with lactic acid, lowering pH and muting the NF‑κB alarm inside macrophages—the very cells that should be calling for help,” explained Dr. Ronni da Silva, Research Scientist at SMART AMR and first author of the paper. “By pinpointing how acidity rewires immune signaling, we now have clear targets to reactivate the immune response.”
What This Means for Treatment Strategies
This research doesn’t offer an immediate cure, but it shifts the focus toward strategies that bolster the immune system rather than solely relying on antibiotics. Potential therapeutic avenues include reducing acidity within the wound environment or blocking the signals that lactic acid uses to suppress immune cells. As Medical Xpress reports, this could lead to therapies that promote more reliable wound healing and reduce the risk of complications.
Professor Kimberly Kline, Principal Investigator at SMART AMR and corresponding author of the study, emphasized the broader implications: “This discovery strengthens our understanding of host-pathogen interactions and offers new directions for developing treatments and wound care that target the bacteria’s immunosuppressive strategies. By revealing how the immune response is shut down, this research may help improve infection management and support better recovery outcomes for patients, especially those with chronic wounds or weakened immunity.”
Next Steps: From Lab to Clinic
The researchers are now planning to validate their findings in additional pathogens and human wound samples. This will be followed by assessments in more advanced preclinical models before any potential clinical trials can be considered. The team also intends to investigate whether similar lactic acid-driven immune suppression mechanisms are at play in other types of infections. This ongoing work aims to translate these fundamental discoveries into tangible improvements in wound care and infection management.