Structure and functions of the Bordetella tracheal cytotoxin.
Of the various toxins and virulence-related factors produced by Bordetella pertussis, only one has been demonstrated to reproduce the specific respiratory epithelial cytopathology characteristic of the pertussis syndrome. That molecule is tracheal cytotoxin (TCT), which is released by B. pertussis during log phase growth. An HPLC-based method has allowed us to purify TCT from culture supernatants, resulting in a preparation with undetectable levels of endotoxin and which is homogeneous by all analytical criteria, including fast atom bombardment-mass spectrometry (FAB-MS). Exposure to purified TCT specifically damages ciliated epithelial cells, causing ciliostasis and extrusion of these cells. Other species of Bordetella, which generate remarkably similar respiratory tract infections and ciliated cell-specific pathology, produce a chemically identical TCT. Compositional analysis and FAB-MS have unambiguously defined the structure of TCT as N-acetylglucosaminyl-1, 6-anhydro-N-acetylmuramylalanyl-gamma-glutamyl-diaminopimelylalanine+ ++. This particular disaccharide-tetrapeptide composition and arrangement reveals that TCT is apparently formed by cleavage of peptidoglycan. Unlike other gram-negative bacteria, however, B. pertussis seems to be very selective in its release of cell wall fragments: greater than 95% of soluble peptidoglycan in culture supernatants is TCT. The structure of TCT places it in the "muramyl peptide" family, a group of structurally related molecules that are responsible for a diverse array of biological activities. Neisseria gonorrhoeae also releases muramyl peptides (one of which is identical to TCT) that can cause ciliated cell-specific damage like that seen during gonococcal infection of fallopian tube mucosa. In addition, TCT is absolutely identical in structure to FSu, a potent sleep-promoting factor isolated from humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Goldman
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Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110.
Cookson
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BT
D000818:Animals; D002923:Cilia / Q000187:drug effects; D003603:Cytotoxins / Q000633:toxicity*; D006801:Humans; D015394:Molecular Structure; D010457:Peptidoglycan / Q000633:toxicity*; D012894:Sleep Stages; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000633:toxicity*
D003603:Cytotoxins; D010457:Peptidoglycan; D010566:Virulence Factors, Bordetella; C059708:tracheal cytotoxin, Bordetella pertussis