Functional mapping of community-acquired respiratory distress syndrome (CARDS) toxin of Mycoplasma pneumoniae defines regions with ADP-ribosyltransferase, vacuolating and receptor-binding activities

Thirumalai R. Kannan, Manickam Krishnan, Kumaraguruparan Ramasamy, Argentina Becker, Olga N. Pakhomova, P. John Hart, Joel B. Baseman

Producción científica: Articlerevisión exhaustiva

24 Citas (Scopus)

Resumen

Community-acquired respiratory distress syndrome (CARDS) toxin from Mycoplasma pneumoniae is a 591-amino-acid virulence factor with ADP-ribosyltransferase (ADPRT) and vacuolating activities. It is expressed at low levels during in vitro growth and at high levels during colonization of the lung. Exposure of experimental animals to purified recombinant CARDS toxin alone is sufficient to recapitulate the cytopathology and inflammatory responses associated with M. pneumoniae infection in humans and animals. Here, by molecular modelling, serial truncations and site-directed mutagenesis, we show that the N-terminal region is essential for ADP-ribosylating activity. Also, by systematic truncation and limited proteolysis experiments we identified a portion of the C-terminal region that mediates toxin binding to mammalian cell surfaces and subsequent internalization. In addition, the C-terminal region alone induces vacuolization in a manner similar to full-length toxin. Together, these data suggest that CARDS toxin has a unique architecture with functionally separable N-terminal and C-terminal domains.

Idioma originalEnglish (US)
Páginas (desde-hasta)568-581
Número de páginas14
PublicaciónMolecular Microbiology
Volumen93
N.º3
DOI
EstadoPublished - ago 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Huella

Profundice en los temas de investigación de 'Functional mapping of community-acquired respiratory distress syndrome (CARDS) toxin of Mycoplasma pneumoniae defines regions with ADP-ribosyltransferase, vacuolating and receptor-binding activities'. En conjunto forman una huella única.

Citar esto