ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogens

Edited by Stanley Falkow, Stanford University, Stanford, CA, and approved March 2, 2006
April 25, 2006
103 (17) 6724-6729

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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Data Availability

Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. DQ447746–DQ447750).

Acknowledgments

We thank Marianna Cagle and Pramod Gowda for technical assistance and Drs. J. J. Coalson, R. L. Reddick, and A. M. Collier for interpretation of histological data. This work was supported by National Institutes of Health Grant AI45737.

Supporting Information

Adobe PDF - 10644NewFig7.pdf
Adobe PDF - 10644NewFig7.pdf

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 103 | No. 17
April 25, 2006
PubMed: 16617115

Classifications

Data Availability

Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. DQ447746–DQ447750).

Submission history

Received: December 12, 2005
Published online: April 25, 2006
Published in issue: April 25, 2006

Keywords

  1. ADP ribosylation
  2. community-acquired respiratory distress syndrome toxin
  3. vacuolization

Acknowledgments

We thank Marianna Cagle and Pramod Gowda for technical assistance and Drs. J. J. Coalson, R. L. Reddick, and A. M. Collier for interpretation of histological data. This work was supported by National Institutes of Health Grant AI45737.

Notes

This paper was submitted directly (Track II) to the PNAS office.

Authors

Affiliations

T. R. Kannan
Department of Microbiology and Immunology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229
Joel B. Baseman [email protected]
Department of Microbiology and Immunology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229

Notes

*To whom correspondence should be addressed. E-mail: [email protected]
Author contributions: T.R.K. and J.B.B. designed research; T.R.K. performed research; T.R.K. and J.B.B. analyzed data; and T.R.K. and J.B.B. wrote the paper.

Competing Interests

Conflict of interest statement: No conflicts declared.

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    ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogens
    Proceedings of the National Academy of Sciences
    • Vol. 103
    • No. 17
    • pp. 6413-6776

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