A Streptomyces tendae Specialized Metabolite Inhibits Quorum Sensing in Group A Streptococcus

Quorum sensing (QS) is a means of Bacterial communication accomplished by microbe-produced signals and sensory systems. QS systems regulate important population-wide behaviors in bacteria, including secondary metabolite production, swarming motility, and bioluminescence. The human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]) utilizes Rgg-SHP QS systems to regulate biofilm formation, protease production, and activation of cryptic competence pathways. Given their reliance on small-molecule signals, QS systems are attractive targets for small-molecule modulators that would then affect gene expression. In this study, a high-throughput luciferase assay was employed to screen an Actinobacteria-derived secondary metabolite (SM) fraction library to identify small molecule inhibitors of Rgg regulation. A metabolite produced by Streptomyces tendae D051 was found to be a general inhibitor of GAS Rgg-mediated QS. Herein, we describe the biological activity of this metabolite as a QS inhibitor. IMPORTANCE Streptococcus pyogenes, a human pathogen known for causing infections such as pharyngitis and necrotizing fasciitis, uses quorum sensing (QS) to regulate social responses in its environment. Previous studies have focused on disrupting QS as a means to control specific Bacterial signaling outcomes. In this work, we identified and described the activity of a naturally derived S. pyogenes QS inhibitor. This study demonstrates that the inhibitor affects three separate but similar QS signaling pathways.

Actinobacteria; Streptococcus; quorum sensing.