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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)568-581
Number of pages14
JournalMolecular Microbiology
Volume93
Issue number3
DOIs
StatePublished - Aug 2014

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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