title: A novel staphylococcal internalization mechanism involves the major autolysin Atl and heat shock cognate protein Hsc70 as host cell receptor.
abstract: Staphylococcus aureus and Staphylococcus epidermidis can cause serious chronic and recurrent infections that are difficult to eradicate. An important pathogenicity factor in these infections caused by S. aureus is its ability to be internalized by non-professional phagocytes thereby evading the host immune system and antibiotic treatment. Here, we report a novel mechanism involved in staphylococcal internalization by host cells, which is mediated by the major autolysin/adhesins Atl and AtlE from S. aureus and S. epidermidis respectively. In a flow cytometric internalization assay, atl and atlE mutants are significantly reduced in their capacities to be internalized by endothelial cells. Moreover, pre-incubation of endothelial cells with recombinant Atl dose-dependently inhibited internalization. As putative Atl-host cell receptor, the heat shock cognate protein Hsc70 was identified by mass spectrometry. The importance of Hsc70 in internalization was demonstrated by the inhibition of S. aureus internalization with anti-Hsc70 antibodies. In conclusion, this novel Atl- or AtlE-mediated internalization mechanism may represent a 'back-up' mechanism in S. aureus internalization, while it may represent the major or even sole mechanism involved in the internalization of coagulase-negative staphylococci and thus may play an important role in the pathogenesis of chronic and relapsing infections with these serious pathogens.
authors.affiliation: Institute of Medical Microbiology, Department of Infectiology, University Hospital of Münster, Münster, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Hirschhausen
authors.forename: Tim
authors.initials: T
authors.lastname: Schlesier
authors.forename: M Alexander
authors.initials: MA
authors.lastname: Schmidt
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
authors.forename: Georg
authors.initials: G
authors.lastname: Peters
authors.forename: Christine
authors.initials: C
authors.lastname: Heilmann
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D042783:Endothelial Cells / Q000382:microbiology; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000378:metabolism; D010587:Phagocytosis; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D013212:Staphylococcus epidermidis / Q000472:pathogenicity*
chemical_list: D018829:Adhesins, Bacterial; D050883:HSC70 Heat-Shock Proteins; D009238:N-Acetylmuramoyl-L-alanine Amidase