Enterococcus faecalis biofilm rewires neutrophil metabolism to suppress antimicrobial functions

Enterococcus faecalis is an opportunistic pathogen that persists in biofilm-associated infections despite robust neutrophil recruitment. How E. faecalis evades neutrophils remains poorly understood. Here, we investigated how E. faecalis biofilms alter effector functions in human neutrophils and a murine wound infection model. We found that E. faecalis biofilm suppresses neutrophil extracellular trap (NET) formation, bacterial engulfment, and neutrophil-mediated control of biofilm growth. This suppression is partly driven by production of lactic acid through the lactate dehydrogenases (LDH) of E. faecalis , which acidifies the extracellular environment, lowers neutrophil intracellular pH, and disrupts glycolysis, the tricarboxylic acid cycle, and the oxidative pentose phosphate pathway. In a murine wound infection model, loss of LDH increased neutrophil recruitment and NETosis. We also found that high bacterial density, a defining feature of biofilms, suppresses NETosis through a lactic acid-independent mechanism. Collectively, these findings identify biofilm immune evasion strategies mediated by bacterial metabolism and the high-density structural organization of biofilm-associated bacteria.