title: Excreted Cytoplasmic Proteins Contribute to Pathogenicity in Staphylococcus aureus.
abstract: Excretion of cytoplasmic proteins in pro- and eukaryotes, also referred to as "nonclassical protein export," is a well-known phenomenon. However, comparatively little is known about the role of the excreted proteins in relation to pathogenicity. Here, the impact of two excreted glycolytic enzymes, aldolase (FbaA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), on pathogenicity was investigated in Staphylococcus aureus Both enzymes bound to certain host matrix proteins and enhanced adherence of the bacterial cells to host cells but caused a decrease in host cell invasion. FbaA and GAPDH also bound to the cell surfaces of staphylococcal cells by interaction with the major autolysin, Atl, that is involved in host cell internalization. Surprisingly, FbaA showed high cytotoxicity to both MonoMac 6 (MM6) and HaCaT cells, while GAPDH was cytotoxic only for MM6 cells. Finally, the contribution of external FbaA and GAPDH to S. aureus pathogenicity was confirmed in an insect infection model.
authors.affiliation: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ebner
authors.affiliation: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Rinker
authors.affiliation: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Minh Thu
authors.initials: MT
authors.lastname: Nguyen
authors.affiliation: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Popella
authors.affiliation: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Mulugeta
authors.initials: M
authors.lastname: Nega
authors.affiliation: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Arif
authors.initials: A
authors.lastname: Luqman
authors.affiliation: Department of Dermatology, University of Tübingen, Tübingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schittek
authors.affiliation: Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
authors.forename: Moreno
authors.initials: M
authors.lastname: Di Marco
authors.affiliation: Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.affiliation: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany friedrich.goetz@uni-tuebingen.de.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001422:Bacterial Adhesion; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D054884:Host-Pathogen Interactions; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D007814:Larva / Q000382:microbiology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D009036:Moths / Q000382:microbiology; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D016019:Survival Analysis; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D016326:Extracellular Matrix Proteins; C078635:fibronectin-binding proteins, bacterial; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D009238:N-Acetylmuramoyl-L-alanine Amidase