title: Epidemiology, variable genetic organization and regulation of the EDIN-B toxin in Staphylococcus aureus from bacteraemic patients.
abstract: EDIN-B (epidermal cell differentiation inhibitor-B; also termed C3Stau) is an exotoxin of Staphylococcus aureus which ADP-ribosylates and inactivates Rho GTP binding proteins. The EDIN-B gene (edin-B) and the gene for exfoliative toxin D (etd) make up the central part of a recently described pathogenicity island. Here we evaluated the prevalence and genetic organization of the edin-B/etd pathogenicity island in invasive S. aureus isolates, and characterized edin-B transcription and EDIN-B production using artificial constructs transduced in S. aureus strains RN6390 and Newman. We found that eight out of 121 (7 %) S. aureus blood culture isolates harbour edin-B, which is organized in three novel variants of the original edin-B/etd pathogenicity island. In the serum of patients infected with edin-B-positive S. aureus, significant titres of anti-EDIN-B antibodies could be detected. Regulation of edin-B transcription depended on the sarA but not on the agr regulatory system. Furthermore, retrieval of EDIN-B protein secreted by S. aureus RN6390 required the presence of alpha2-macroglobulin to inhibit the activity of extracellular proteases. These data suggest that the EDIN-B toxin is produced during human infection, is part of a highly variable pathogenicity island and can be controlled by the sarA gene regulon and secreted bacterial proteases.
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, University Medical Center Hamburg-Eppendorf, Martinistraße52, 20246 Hamburg, Germany.
authors.forename: Gefion C
authors.initials: GC
authors.lastname: Franke
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, University Medical Center Hamburg-Eppendorf, Martinistraße52, 20246 Hamburg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Böckenholt
authors.affiliation: Department of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Sugai
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, University Medical Center Hamburg-Eppendorf, Martinistraße52, 20246 Hamburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Rohde
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, University Medical Center Hamburg-Eppendorf, Martinistraße52, 20246 Hamburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Aepfelbacher
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism*; D000907:Antibodies, Bacterial / Q000097:blood; D004269:DNA, Bacterial / Q000235:genetics; D005083:Exfoliatins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D005838:Genotype; D006801:Humans; D018085:Regulon; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification; D014158:Transcription, Genetic
chemical_list: D000907:Antibodies, Bacterial; D004269:DNA, Bacterial; D005083:Exfoliatins; D036002:ADP Ribose Transferases; C479830:C3stau2 protein, Staphylococcus aureus