Hidden drivers of heart infections
Loss of Fsr quorum sensing promotes biofilm formation and worsens outcomes in enterococcal infective endocarditis
SUMMARY
Infective endocarditis (IE) is a severe heart infection caused predominantly by Gram-positive bacteria forming biofilm on heart valves. While biofilm formation is central to disease progression, the underlying bacterial mechanisms remain poorly understood. Here, the authors identify the Fsr quorum sensing (QS) system of Enterococcus faecalis as an unexpected negative regulator of biofilm and pathogenesis in IE. Using microfluidic and in vivo models, they show that blood flow prevents Fsr activation in early IE, with Fsr induction occurring only later, once bacteria form biofilm microcolonies and become shielded from flow. Deletion of Fsr promotes robust biofilm growth, driven partly through the downregulation of GelE and SprE proteases, reprograms metabolism by upregulating lrgAB to enhance pyruvate utilisation, and increases gentamicin tolerance in vivo. Furthermore, they show that GelE cleaves the human pro-IL-1β into an active form, suggesting a species-specific mechanism for inflammation modulation by QS. In support of these findings, analysis of IE patient cohorts shows that naturally occurring Fsr-deficient E. faecalis strains are associated with prolonged bacteremia. Overall, these findings provide insights into how host blood flow impacts QS activation, which, in turn, regulates pathogenesis in IE, and highlight the Fsr QS as a potential determinant of clinical disease course.
Full article: https://doi.org/10.1038/s41467-026-68366-8
WHY IS THIS IMPORTANT?
Heart valve infections are difficult to cure because bacteria hide in biofilms that resist antibiotics. This study reveals that E. faecalis can grow more aggressively when it loses a key communication pathway (Fsr quorum sensing). Blood flow initially keeps this system turned off, allowing bacteria to build biofilms. When Fsr is missing, bacteria grow faster, adapt their metabolism, and survive antibiotics more easily. Patient data confirm that strains lacking this system are linked to longer-lasting infections. Understanding how bacteria respond to the heart valve environment helps explain treatment failure and may guide better strategies for managing infective endocarditis.