Loss of Fsr quorum sensing promotes biofilm formation and worsens outcomes in enterococcal infective endocarditis.

ABSTRACT: 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, we 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, we 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

SUBMITTER: Antypas H 

PROVIDER: S-EPMC12909850 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature