ADP-Ribosylating and Vacuolating Cytotoxin of Mycoplasma pneumoniae Represents Unique Virulence Determinant among Bacterial Pathogens

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 17; pp. 6724 - 6729
• Main Authors: Kannan, T. R., Baseman, Joel B.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25.04.2006
• Subjects: Adenosine Diphosphate Ribose - metabolism; ADP Ribose Transferases - genetics; ADP Ribose Transferases - metabolism; ADP Ribose Transferases - toxicity; Amino Acid Sequence; Amino acids; Animals; Antibodies, Bacterial - blood; Art exhibitions; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacterial Proteins - toxicity; Biological Sciences; CHO Cells; Community-Acquired Infections - immunology; Community-Acquired Infections - microbiology; Cricetinae; Cytotoxins - genetics; Cytotoxins - metabolism; Cytotoxins - toxicity; Epithelial cells; Genes, Bacterial; HeLa cells; Humans; Infections; Microbiology; Molecular Sequence Data; Mutagenesis, Site-Directed; Mycoplasma; Mycoplasma pneumoniae; Mycoplasma pneumoniae - genetics; Mycoplasma pneumoniae - metabolism; Mycoplasma pneumoniae - pathogenicity; Organ Culture Techniques; Papio; Pathogens; Pneumonia; Pneumonia, Mycoplasma - immunology; Pneumonia, Mycoplasma - microbiology; Polymorphism, Genetic; Proteins; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Recombinant Proteins - toxicity; Respiratory Distress Syndrome, Adult - immunology; Respiratory Distress Syndrome, Adult - microbiology; Sequence Homology, Amino Acid; Toxins; Trachea - drug effects; Trachea - pathology; Virulence; Virulence Factors - genetics; Virulence Factors - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0510644103

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.