title: Functional analysis of the group A streptococcal luxS/AI-2 system in metabolism, adaptation to stress and interaction with host cells.
abstract: BACKGROUND
  The luxS/AI-2 signaling pathway has been reported to interfere with important physiological and pathogenic functions in a variety of bacteria. In the present study, we investigated the functional role of the streptococcal luxS/AI-2 system in metabolism and diverse aspects of pathogenicity including the adaptation of the organism to stress conditions using two serotypes of Streptococcus pyogenes, M1 and M19.
  
  
  RESULTS
  Exposing wild-type and isogenic luxS-deficient strains to sulfur-limited media suggested a limited role for luxS in streptococcal activated methyl cycle metabolism. Interestingly, loss of luxS led to an increased acid tolerance in both serotypes. Accordingly, luxS expression and AI-2 production were reduced at lower pH, thus linking the luxS/AI-2 system to stress adaptation in S. pyogenes. luxS expression and AI-2 production also decreased when cells were grown in RPMI medium supplemented with 10% serum, considered to be a host environment-mimicking medium. Furthermore, interaction analysis with epithelial cells and macrophages showed a clear advantage of the luxS-deficient mutants to be internalized and survive intracellularly in the host cells compared to the wild-type parents. In addition, our data revealed that luxS influences the expression of two virulence-associated factors, the fasX regulatory RNA and the virulence gene sibA (psp).
  
  
  CONCLUSIONS
  Here, we suggest that the group A streptococcal luxS/AI-2 system is not only involved in the regulation of virulence factor expression but in addition low level of luxS expression seems to provide an advantage for bacterial survival in conditions that can be encountered during infections.
authors.affiliation: University of Vienna, Department of Microbiology and Immunobiology, 1030 Vienna, Austria. maria.siller@univie.ac.at
authors.forename: Maria
authors.initials: M
authors.lastname: Siller
authors.forename: Rajendra P
authors.initials: RP
authors.lastname: Janapatla
authors.forename: Zaid A
authors.initials: ZA
authors.lastname: Pirzada
authors.forename: Christine
authors.initials: C
authors.lastname: Hassler
authors.forename: Daniela
authors.initials: D
authors.lastname: Zinkl
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charpentier
mesh_terms: D000143:Acids / Q000494:pharmacology; D000222:Adaptation, Physiological; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D013437:Carbon-Sulfur Lyases / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D017353:Gene Deletion; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology; D050296:Microbial Viability; D008969:Molecular Sequence Data; D015398:Signal Transduction; D013297:Streptococcus pyogenes / Q000235:genetics / Q000502:physiology*; D024363:Transcription Initiation Site; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D000143:Acids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D037521:Virulence Factors; D006714:Homoserine; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria