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@viollierpat.bsky.social @eckerleisabella.bsky.social

Together, this work shows E. faecalis to be a master manipulator of innate immunity, capable of actively reprogramming innate immune cell function. The consequence is enhanced persistence and augmented mono- and polymicrobial biofilm-associated infections. 🐁

It also explains an observation by Patrick Kao where E. faecalis suppresses S. aureus-induced NETosis. academic.oup.com/femsmicrobes.... And may speak to @claudiajades.bsky.social observation that E. faecalis turn neutrophils into llittle replication factories! journals.asm.org/doi/10.1128/....

This is a nice parallel to recent work from @ronni.bsky.social, showing how E. faecalis lactic acid suppresses macrophage activation. www.cell.com/cell-host-mi...

Enterococcus faecalis-derived lactic acid suppresses macrophage activation to facilitate persistent and polymicrobial wound infectionsda Silva et al. show that Enterococcus faecalis-derived lactic acid suppresses macrophage NF-κB activation via MCT-1 and GPR81 signaling. This lactic-acid-driven immunosuppression promotes bacterial p...www.cell.com

Haris talks more about his work @scelse.bsky.social here: youtu.be/NmoJQSpmkF8

Naturally occurring QS chromosomal deletions have long been observed in E. faecalis clinical isolates - without a clear functional explanation. Now, in collaboration with the teams of @dariavantyne.bsky.social 🇺🇸 & Annelies Zinkernagel 🇨🇭, we link these deletions to increased IE disease severity. 💡

Haris found that blood flow suppresses Fsr early in infection and that QS activation occurs only after bacteria form flow-shielded microcolonies. Strikingly, absence of Fsr QS conferred unchecked biofilm growth and metabolic rewiring, driving antibiotic tolerance, and prolonged bacteremia. 🤯

Great 3 continent team effort including Brenda Tien, Patrick Kao, Jianzhu Chen and BlueSkyers @harisantypas.bsky.social @cenkcelik.bsky.social @gthibault.bsky.social @scelse.bsky.social

I remember well this very cool study by @kayla-king.bsky.social et al. Thanks for highlighting the possible link to our work here!

What’s next? Big questions we're excited about: • How does Ef hijack intracellular trafficking machinery for its replication? • What host pathways define “permissive” vs “restrictive” intracellular states? • How does intracellular replication impact chronicity/relapse in vivo? Stay tuned...🧐 6/6

There's more! @frederickreinhart.bsky.social now shows Fsr quorum sensing turns on during intracellular replication, driving GelE-dependent host cell lysis/egress, a model for how intracellular “factories” become new extracellular inocula, primed for reinfection. 5/n www.biorxiv.org/content/10.6...

Gelatinase regulates the egress of intracellular replicating populations during Enterococcus faecalis infectionEnterococcus faecalis is a common opportunistic pathogen, frequently isolated from chronic wounds, yet the mechanisms underlying its virulence and persistence in this niche remain incompletely underst...www.biorxiv.org

Now, @claudiajades.bsky.social shows that E. faecalis replicates robustly in primary mouse AND human neutrophils - cells we typically think of as executioners, not incubators. 4/n #IAI @asm.org journals.asm.org/doi/10.1128/...

Enterococcus faecalis persists and replicates intracellularly within neutrophils | Infection and ImmunityChronic wound infection represents a major global public health concern, impacting both healthcare costs and patient quality of life (1, 2). Enterococcus faecalis is a Gram-positive opportunistic pathogen associated with infections in a range of contexts, including urinary tract infection, endocarditis, neonatal sepsis, and chronic wound infection (3–7). A facultative anaerobic bacterium and commensal of the human gastrointestinal tract, E. faecalis exhibits both intrinsic and acquired antibiotic resistance (8), making these infections inherently and increasingly difficult to treat. Long considered an extracellular pathogen, E. faecalis aggregates and forms biofilms, enhancing its persistence capacity in chronic infections (9). However, increasing evidence across a range of host cell types points to an intracellular niche and lifestyle of this multifaceted persistent bacterium (10–13).journals.asm.org

In parallel, the team of Pascale Serror and Cristel Archambaud showed E. faecalis can also survive/divide in hepatocytes, forming intracellular clusters (and supporting the “intracellular niche” concept beyond classic phagocytes). 3/n www.tandfonline.com/doi/10.1080/...

The unforeseen intracellular lifestyle of Enterococcus faecalis in hepatocytesEnterococcus faecalis is a bacterial species present at a subdominant level in the human gut microbiota. This commensal turns into an opportunistic pathogen under specific conditions involving dysb...www.tandfonline.com

First, work from @ronni.bsky.social in our group showed E. faecalis can replicate inside macrophages + epithelial cells, and that the intracellularly “trained” population is primed for more efficient reinfection. 2/n #PLOSPathogens @plos.org dx.plos.org/10.1371/jour...

Enterococcus faecalis alters endo-lysosomal trafficking to replicate and persist within mammalian cellsAuthor summary Enterococcus faecalis is often isolated from chronic wounds. Prior to this study, E. faecalis has been observed within different cell types, suggesting that it can successfully colonize...dx.plos.org

The consequence: A rapid, phenotype-first membrane “hardening” unintentionally primes the cell for the mutations that lock in high-level resistance. Sometimes evolution doesn’t wait. E. faeecalis rehearses the phenotypic resistance program before writing it into the genome. 😎

The driver? LTA synthase, which boosts glycolipids when the cell senses membrane damage. The sensor network? LiaFSR + SapRS + BsrRS, working together to flip the switch on this lipid remodeling program.

New work from @colomer-winter.bsky.social shows that E. faecalis doesn’t wait for mutations at all - it immediately rewires its membrane lipids as a stress response to daptomycin. And surprisingly, the cell ends up looking a lot like a resistant strain before any genetic change happens.

@joeyzacks.bsky.social @dariavantyne.bsky.social @maribyndloss.bsky.social

Congratulations! 🤩

Yay yay! Congratulations!!