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Peer-reviewedCC BYScience Advances

Enterococcus faecalis biofilm rewires neutrophil metabolism to suppress antimicrobial activity

  • Haris Antypas1
  • Ronni Anderson Gonçalves da Silva1,2
  • Geneve Kang Xin Wong1
  • Cui Liang2
  • Logeshwari Muthualagu Natarajan1
  • Rachel Jing Wen Tan1
  • Cheryl Jia Yi Neo1
  • Siu Ling Wong3,4
  • Kimberly A. Kline1,2,5
5 affiliations
  1. 1Singapore Centre for Environmental Life Sciences Engineering, School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
  2. 2Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore.
  3. 3Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
  4. 4Tan Tock Seng Hospital, Singapore.
  5. 5Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
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Abstract

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 (LDHs) 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.

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Cite

BibTeXRIS
BibTeX
@article{antypas2026enterococcus,
  title = {{Enterococcus faecalis biofilm rewires neutrophil metabolism to suppress antimicrobial activity}},
  author = {Haris Antypas and Ronni Anderson Gonçalves da Silva and Geneve Kang Xin Wong and Cui Liang and Logeshwari Muthualagu Natarajan and Rachel Jing Wen Tan and Cheryl Jia Yi Neo and Siu Ling Wong and Kimberly A. Kline},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aej4153},
  url = {https://www.science.org/doi/10.1126/sciadv.aej4153},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Enterococcus faecalis biofilm rewires neutrophil metabolism to suppress antimicrobial activity
AU  - Haris Antypas
AU  - Ronni Anderson Gonçalves da Silva
AU  - Geneve Kang Xin Wong
AU  - Cui Liang
AU  - Logeshwari Muthualagu Natarajan
AU  - Rachel Jing Wen Tan
AU  - Cheryl Jia Yi Neo
AU  - Siu Ling Wong
AU  - Kimberly A. Kline
PY  - 2026
DA  - 2026/10/21
JO  - Science Advances
DO  - 10.1126/sciadv.aej4153
UR  - https://www.science.org/doi/10.1126/sciadv.aej4153
AB  - 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 (LDHs) 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.
SN  - 2375-2548
ER  -