THE INTEGRATION OF HOST-GROUP A STREPTOCOCCAL SIGNALS LEADS TO BACTERIAL NICH DOMINANCE

Emanuel Hanski ^1,3 Baruch B. Hertzog ^1,3 Yael Kaufman ^1,3 Debabrata Biswas ^2,4 Miriam Ravins ^1,3 Poornima Ambalavanan ^2,4 Veronique Angeli ^2,4 Swaine L. Chen ^2,4

¹Microbiology and Molecular Genetics, The Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel
²Center for Research Excellence & Technological Enterprise (CREATE), National University of Singapore (NUS)-The Hebrew University of Jerusalem (HUJI), Mechanism of Inflammation Program, Singapore, Singapore
³Microbiology and Molecular Genetics, The Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem Israel, Jerusalem, Israel

Bacteria use quorum-sensing (QS) to regulate gene expression upon generating and sensing autoinducers. We identified a group A Streptococcus (GAS) strain possessing the QS system sil, which produces functional bacteriocins, through a sequential signaling pathway integrating host and bacterial signals. GAS associated with host cells, induces formation and senses asparagine (ASN), that upregulates the expression of the sil autoinducer peptide-SilCR. This consequently switches on the autoinduction cycle of SilCR production. The autoinduction process propagates throughout the GAS population, resulting in synchronous production of bacteriocins. The sequential host-bacterial signal transduction process occurs also in vivo. In accordance, subcutaneous co-injection of mice with the bacteriocin-producing strain and the globally disseminated M1T1 GAS clone results in disappearance of M1T1 from the fascia. The described mechanism explains how a fraction of a bacterial population, in close proximity to host cells, imposes its output signaling on the entire bacterial community.