Gelatinase regulates the egress of intracellular replicating populations during <i>Enterococcus faecali</i>s infection

Article Article scientifique Article Gelatinase regulates the egress of intracellular replicating populations during <i>Enterococcus faecali</i>s infection eng 2026-03-10 2026-03 author Tanoto Frederick Reinhart Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.,Interdisciplinary Graduate Programme, Nanyang Technological University, Singapore, Singapore. author Liew Jia Hui School of Biological Sciences, Nanyang Technological University, Singapore, Singapore. author Stocks Claudia J Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.,Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. author Rawat Deepti Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 410726 Département de microbiologie et médecine moléculaire (MIMOL) author Chong Kelvin Kian Long Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore. author Pethe Kevin Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.,Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.,Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore.,National Center for Infectious Diseases (NCID), Singapore, Singapore. author Antypas Haris Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore. author Kline Kimberly Ann 0000-0002-5472-3074 Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.,School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.,Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore. 984962 Département de microbiologie et médecine moléculaire (MIMOL) e1013738 10.1371/journal.ppat.1013738 41805723 1553-7366 PMC12994788 Enterococcus faecalis is a common opportunistic pathogen, frequently isolated from chronic wounds, yet the mechanisms underlying its virulence and persistence in this niche remain incompletely understood. We previously showed that a subpopulation of E. faecalis can survive intracellularly for several days during murine wound infection and can replicate within macrophages, revealing an unexpected intracellular phase for this traditionally extracellular bacterium. Here, we identify the secreted metalloprotease gelatinase (GelE) and its regulator, the Fsr quorum sensing system, as key modulators of E. faecalis intracellular survival and replication. Mechanistically, Fsr quorum sensing is induced during intracellular replication, promoting GelE-dependent host cell lysis and bacterial egress. In the absence of active GelE, E. faecalis accumulates as large intracellular clusters, a phenotype observed consistently across GelE-deficient wound isolates. In a mouse wound model, GelE-deficient E. faecalis similarly exhibited higher intracellular numbers within wound infection-associated host cells. Together, our study uncovers GelE as a central effector that orchestrates the transition between intracellular and extracellular lifestyles of E. faecalis, providing a possible explanation for its persistence in chronic wound infection. Enterococcus faecalis / pathogenicity Enterococcus faecalis / enzymology Enterococcus faecalis / growth & development Animals Mice Gelatinases / metabolism Gelatinases / genetics Gram-Positive Bacterial Infections / microbiology Gram-Positive Bacterial Infections / pathology Gram-Positive Bacterial Infections / enzymology Bacterial Proteins / metabolism Bacterial Proteins / genetics Quorum Sensing / physiology Macrophages / microbiology Wound Infection / microbiology Humans Virulence Mice, Inbred C57BL Dewey 616 Swiss National Science Foundation The Cell Biology of Enterococcus faecalis Infection 212262 CH 54 Département de microbiologie et médecine moléculaire 21B false 1396 Pathogenesis of biofilm-associated infections 1044 PLOS pathogens 22 3 0dfe0f8a-1b4a-45d6-9dc7-c99228cfd1c5 Article (Published version) Public journal.ppat.1013738.pdf 2777065 application/pdf CC BY-4.0 02963c65d0104e8ce68ece73027a76050b079598ae2ca113de833f4909f4c80e 5f0d1b96-a065-4710-b4eb-78620998af12 Supplemental data Public 10_1371_journal_ppat_1013738.zip 31215301 application/zip 7e158e37669ba164e30791256abc1540d1c74dc9af3cb6d2b546e8f7111ed30a openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

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Gelatinase regulates the egress of intracellular replicating populations during Enterococcus faecalis infection	PLOS pathogens			2026	9	134

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