6533b821fe1ef96bd127ae5b
RESEARCH PRODUCT
Pore-forming Staphylococcus aureus alpha-toxin triggers epidermal growth factor receptor-dependent proliferation.
Shabnam ShaidErik BeckmannSucharit BhakdiSaskia BiehlWiesia BobkiewiczKatrin DerschGunnaporn VeerachatoMatthias HusmannShan-rui HanUlrike Haugwitzsubject
KeratinocytesStaphylococcus aureusSrc Homology 2 Domain-Containing Transforming Protein 1ImmunologyCellBacterial ToxinsBlotting WesternFluorescent Antibody TechniqueTransfectionMicrobiologyCell LineHemolysin ProteinsDownregulation and upregulationNucleated cellVirologymedicineHumansGrowth factor receptor inhibitorEpidermal growth factor receptorStaphylococcus aureus alpha toxinAdaptor Proteins Signal TransducingCell Line TransformedCell ProliferationbiologyCytotoxinsReverse Transcriptase Polymerase Chain ReactionGene Expression ProfilingCell CycleCell cycleFlow CytometryTransmembrane proteinCell biologyErbB Receptorsmedicine.anatomical_structureShc Signaling Adaptor Proteinsbiology.proteinMitogensSignal Transductiondescription
Staphylococcal alpha-toxin is an archetypal killer protein that homo-oligomerizes in target cells to create small transmembrane pores. The membrane-perforating beta-barrel motif is a conserved attack element of cytolysins of Gram-positive and Gram-negative bacteria. Following the recognition that nucleated cells can survive membrane permeabilization, a profile of abundant transcripts was obtained in transiently perforated keratinocytes. Several immediate early genes were found to be upregulated, reminiscent of the cellular response to growth factors. Cell cycle analyses revealed doubling of S + G2/M phase cells 26 h post toxin treatment. Determination of cell counts uncovered that after an initial drop, numbers increased to exceed the controls after 2 days. A non-lytic alpha-toxin mutant remained without effect. The alpha-toxin pore is too small to allow egress of cytosolic growth factors, and evidence was instead obtained for growth signalling via the epidermal growth factor receptor (EGFR). Inhibition of the EGFR or of EGFR-proligand-processing blocked the mitogenic effect of alpha-toxin. Western blots with phospho-specific antibodies revealed activation of the EGFR, and of the adapter protein Shc. Immediate early response and proliferation upon transient plasma membrane pore formation by bacterial toxins may represent a novel facet of the complex interaction between pathogen and host.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2006-09-21 | Cellular microbiology |