title: Inhibitory role of acyl homoserine lactones in hemolytic activity and viability of Streptococcus pyogenes M6 S165.
abstract: Streptococcus pyogenes an adapted human pathogen asymptomatically colonizes the nasopharynx, among other polymicrobial communities. However, information on the events leading to the colonization and expression of virulence markers subject to interspecies and host-bacteria interactions are limited. The interference of acyl homoserine lactones (AHLs) with the hemolytic activity and viability of S. pyogenes M6 S165 was examined. AHLs, with fatty acid side chains ≥12 carbon atoms, inhibited hemolytic activity by downregulating the expression of the sag operon involved in the production of streptolysin S. Inhibitory AHLs upregulated the expression of transcriptional regulator LuxR. Electrophoretic mobility shift assays revealed the interaction of LuxR with the region upstream of sagA. AHL-mediated bactericidal activity observed at higher concentrations (mM range) was an energy-dependent process, constrained by the requirement of glucose and iron. Ferrichrome transporter FtsABCD facilitated transport of AHLs across the streptococcal membrane. The study demonstrates a previously unreported role for AHLs in S. pyogenes virulence.
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Sunil D
authors.initials: SD
authors.lastname: Saroj
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Holmer
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Júlia M
authors.initials: JM
authors.lastname: Berengueras
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Ann-Beth
authors.initials: AB
authors.lastname: Jonsson
mesh_terms: D054742:Acyl-Butyrolactones / Q000494:pharmacology*; D052978:Disk Diffusion Antimicrobial Tests; D004305:Dose-Response Relationship, Drug; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D007501:Iron / Q000378:metabolism; D050296:Microbial Viability / Q000187:drug effects; D009876:Operon; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013297:Streptococcus pyogenes / Q000145:classification / Q000187:drug effects* / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D054742:Acyl-Butyrolactones; D012097:Repressor Proteins; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins; D007501:Iron