@article{9e2cae32b25a49b0a957b50dbda583d0,
title = "Disulfide bond of Mycoplasma pneumoniae community-acquired respiratory distress syndrome toxin is essential to maintain the ADP-ribosylating and vacuolating activities",
abstract = "Mycoplasma pneumoniae is the leading cause of bacterial community-acquired pneumonia among hospitalised children in United States and worldwide. Community-acquired respiratory distress syndrome (CARDS) toxin is a key virulence determinant of M. pneumoniae. The N-terminus of CARDS toxin exhibits ADP-ribosyltransferase (ADPRT) activity, and the C-terminus possesses binding and vacuolating activities. Thiol-trapping experiments of wild-type (WT) and cysteine-to-serine-mutated CARDS toxins with alkylating agents identified disulfide bond formation at the amino terminal cysteine residues C230 and C247. Compared with WT and other mutant toxins, C247S was unstable and unusable for comparative studies. Although there were no significant variations in binding, entry, and retrograde trafficking patterns of WT and mutated toxins, C230S did not elicit vacuole formation in intoxicated cells. In addition, the ADPRT domain of C230S was more sensitive to all tested proteases when compared with WT toxin. Despite its in vitro ADPRT activity, the reduction of C230S CARDS toxin-mediated ADPRT activity-associated IL-1β production in U937 cells and the recovery of vacuolating activity in the protease-released carboxy region of C230S indicated that the disulfide bond was essential not only to maintain the conformational stability of CARDS toxin but also to properly execute its cytopathic effects.",
keywords = "ADP-ribosylation, CARDS toxin, disulfide bond, mycoplasma, vacuolation",
author = "Sowmya Balasubramanian and Lavanya Pandranki and Suzanna Maupin and Kumaraguruparan Ramasamy and Taylor, {Alexander B.} and Hart, {Peter John} and Baseman, {Joel B.} and Kannan, {Thirumalai R.}",
note = "Funding Information: This research was supported by National Institutes of Health ‐ National Institute of Allergy and Infectious Diseases (NIH‐NIAID) grants AI 141877 (to T. R. K.), U19AI070412 (to J. B. B), and The Welch Foundation grant AQ‐1399 (to P. J. H.). The University of Texas Health Science Center at San Antonio's X‐Ray Crystallography Core Laboratory in the Institutional Research Cores is supported by the Office of the Vice President for Research and by the Mays Cancer Center National Institutes of Health ‐ National Cancer Institute (NIH/NCI) grant P30 CA054174. Funding Information: This research was supported by National Institutes of Health - National Institute of Allergy and Infectious Diseases (NIH-NIAID) grants AI 141877 (to T.?R.?K.), U19AI070412 (to J.?B.?B), and The Welch Foundation grant AQ-1399 (to P.?J.?H.). The University of Texas Health Science Center at San Antonio's X-Ray Crystallography Core Laboratory in the Institutional Research Cores is supported by the Office of the Vice President for Research and by the Mays Cancer Center National Institutes of Health - National Cancer Institute (NIH/NCI) grant P30 CA054174. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. Funding Information: National Institutes of Health ‐ National Institute of Allergy and Infectious Diseases, Grant/Award Numbers: AI141877 and U19AI070412; National Institutes of Health ‐ National Cancer Institute, Grant/Award Number: P30 CA054174 awarded to the Mays Cancer Center; The Welch Foundation, Grant/Award Number: AQ‐1399; Office of the Vice President for Research, University of Texas Health San Antonio Publisher Copyright: {\textcopyright} 2019 John Wiley & Sons Ltd",
year = "2019",
month = aug,
doi = "10.1111/cmi.13032",
language = "English (US)",
volume = "21",
journal = "Cellular Microbiology",
issn = "1462-5814",
publisher = "Wiley-Blackwell",
number = "8",
}