title: Role of CsrR, hyaluronic acid, and SpeB in the internalization of Streptococcus pyogenes M type 3 strain by epithelial cells.
abstract: Internalization of group A streptococcus by human epithelial cells has been extensively studied during the past 6 years. It is now clear that multiple mechanisms are involved in this process. We have previously demonstrated that the CsrR global regulator controls the internalization of an invasive M type 3 strain through regulation of the has (hyaluronic acid synthesis) operon, as well as another, unknown gene(s). Recently, it was reported that the CsrR-regulated cysteine protease (SpeB) is also involved in bacterial uptake. In this study we have examined the roles of CsrR, hyaluronic acid capsule, and SpeB in streptococcal internalization. We have constructed isogenic mutants of the M3 serotype deficient in the csrR, hasA, and speB genes and tested their ability to be internalized by HEp-2 epithelial cells. Inactivation of csrR abolished internalization, while inactivation of either hasA or speB increased the internalization efficiency. Mutation in csrR derepressed hasA transcription and lowered the activity of SpeB, while no effect on speB transcription was observed. The speB mutant expressed smaller amounts of capsule, while the hasA mutant transcribed more csrR and speB mRNAs. Thus, it seems that complex interactions between CsrR, SpeB, and capsule are involved in modulation of group A streptococcus internalization.
authors.affiliation: Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Jeries
authors.initials: J
authors.lastname: Jadoun
authors.forename: Osnat
authors.initials: O
authors.lastname: Eyal
authors.forename: Shlomo
authors.initials: S
authors.lastname: Sela
mesh_terms: D000595:Amino Acid Sequence; D016667:Bacterial Capsules / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004269:DNA, Bacterial; D004705:Endocytosis / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D014453:Glucuronosyltransferase / Q000235:genetics / Q000276:immunology*; D016695:Glycosyltransferases; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000235:genetics / Q000276:immunology*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016296:Mutagenesis; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D017422:Sequence Analysis, DNA; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014158:Transcription, Genetic; D014166:Transferases; D014407:Tumor Cells, Cultured; D029867:Xenopus Proteins
chemical_list: D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D015853:Cysteine Proteinase Inhibitors; D004269:DNA, Bacterial; D008565:Membrane Proteins; D012097:Repressor Proteins; D029867:Xenopus Proteins; D006820:Hyaluronic Acid; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases; D003546:Cysteine Endopeptidases; C042477:streptopain; D007930:Leucine; C024974:E 64