Functional mapping of community‐acquired respiratory distress syndrome (CARDS) toxin of Mycoplasma pneumoniae defines regions with ADP‐ribosyltransferase,vacuolating and receptor‐binding activities |
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| Authors: | Thirumalai R Kannan Manickam Krishnan Kumaraguruparan Ramasamy Argentina Becker Olga N Pakhomova P John Hart Joel B Baseman |
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| Institution: | 1. Department of Microbiology and Immunology/Center for Airway Inflammation Research, The University of Texas Health Science Center at San Antonio, , San Antonio, TX, 78229 USA;2. Department of Biochemistry, The University of Texas Health Science Center at San Antonio, , San Antonio, TX, 78229 USA;3. Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs, South Texas Veterans Health Care System, , San Antonio, TX, 78229 USA |
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| 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. |
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