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ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogens. Proc Nat Acad Sci USA

Department of Microbiology and Immunology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 05/2006; 103(17):6724-9. DOI: 10.1073/pnas.0510644103
Source: PubMed

ABSTRACT Unlike many bacterial pathogens, Mycoplasma pneumoniae is not known to produce classical toxins, and precisely how M. pneumoniae injures the respiratory epithelium has remained a mystery for >50 years. Here, we report the identification of a virulence factor (MPN372) possibly responsible for airway cellular damage and other sequelae associated with M. pneumoniae infections in humans. We show that M. pneumoniae MPN372 encodes a 68-kDa protein that possesses ADP-ribosyltransferase (ART) activity. Within its N terminus, MPN372 contains key amino acids associated with NAD binding and ADP-ribosylating activity, similar to pertussis toxin (PTX) S1 subunit (PTX-S1). Interestingly, MPN372 ADP ribosylates both identical and distinct mammalian proteins when compared with PTX-S1. Remarkably, MPN372 elicits extensive vacuolization and ultimate cell death of mammalian cells, including distinct and progressive patterns of cytopathology in tracheal rings in organ culture that had been previously ascribed to infection with WT virulent M. pneumoniae. We observed dramatic seroconversion to MPN372 in patients diagnosed with M. pneumoniae-associated pneumonia, indicating that this toxin is synthesized in vivo and possesses highly immunogenic epitopes.

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    • "The N-terminal region of CARDS toxin shares limited identity with the catalytic domain of many ADPRT toxins (Kannan and Baseman, 2006). To detect protein scaffolds compatible with the CARDS toxin amino acid sequence, we used the program HHPRED and the entire CARDS toxin amino acid sequence as the query. "
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    • "It possesses only a minor ability to injure respiratory epithelial cells by producing an excess of activated oxygen within the infected cells [for review, see Waites & Talkington, 2004]. Recent evidence has shown that M. pneumoniae produces the community acquired respiratory distress syndrome toxin, but its pathogenic role in human illness still remains to be elucidated [Hardy et al., 2009; Kannan & Baseman, 2006]. Nevertheless, M. pneumoniae is a major pathogen of primary atypical pneumonia as well as a number of extrapulmonary diseases. "
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    • "This pathogenic mycoplasma utilizes multiple adherence mechanisms to colonize and invade airway cells, leading to loss of respiratory epithelium integrity, decreased ciliary movement, and increased cellular vacuolation and exfoliation (Carson et al., 1979, Collier et al., 1983, Tyron et al., 1992, Baseman, 1993, Krause et al., 2001, Balasubramanian et al., 2009). Recently, we identified an ADP ribosylating and vacuolating toxin in M. pneumoniae that can reproduce the cytopathology phenotype associated with mycoplasma infection (Kannan et al., 2006, Hardy et al., 2009). In addition to the overt histopathology that accompanies M. pneumoniae infection, we earlier described alterations in host metabolism that precede and parallel "
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