title: Mutation of luxS affects growth and virulence factor expression in Streptococcus pyogenes.
abstract: Adaptive responses of bacteria that involve sensing the presence of other bacteria are often critical for proliferation and the expression of virulence characteristics. The autoinducer II (AI-2) pathway has recently been shown to be a mechanism for sensing other bacteria that is highly conserved among diverse bacterial species, including Gram-positive pathogens. However, a role for this pathway in the regulation of virulence factors in Gram-positive pathogens has yet to be established. In this study, we have inactivated luxS, an essential component of the AI-2 pathway, in the Gram-positive pathogen Streptococcus pyogenes. Analyses of the resulting mutants revealed the aberrant expression of several virulence properties that are regulated in response to growth phase, including enhanced haemolytic activity, and a dramatic reduction in the expression of secreted proteolytic activity. This latter defect was associated with a reduced ability to secrete and process the precursor of the cysteine protease (SpeB) as well as a difference in the timing of expression of the protease. Enhanced haemolytic activity of the luxS strain was also shown to be linked with an increased expression of the haemolysin S-associated gene sagA. Disruptions of luxS in these mutants also produced a media-dependent growth defect. Finally, an allelic replacement analysis of an S. pyogenes strain with a naturally occurring insertion of IS1239 in luxS suggested a mechanism for modulation of virulence during infection. Results from this study suggest that luxS makes an important contribution to the regulation of S. pyogenes virulence factors.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, Box 8230, St Louis, MO 63110-1093, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Lyon
authors.forename: J C
authors.initials: JC
authors.lastname: Madden
authors.forename: J C
authors.initials: JC
authors.lastname: Levin
authors.forename: J L
authors.initials: JL
authors.lastname: Stein
authors.forename: M G
authors.initials: MG
authors.lastname: Caparon
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D013437:Carbon-Sulfur Lyases; D003470:Culture Media; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006714:Homoserine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000378:metabolism; D009154:Mutation; D013297:Streptococcus pyogenes / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D013301:Streptolysins / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; D005656:Fungal Proteins; D007783:Lactones; C091088:N-octanoylhomoserine lactone; C118425:SAGA protein, Emericella nidulans; D013301:Streptolysins; C026050:streptolysin S; D006714:Homoserine; D003546:Cysteine Endopeptidases; C042477:streptopain; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria