Adenylate cyclase toxin in virulence of the pertussis agent
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F25%3A00643268" target="_blank" >RIV/61388971:_____/25:00643268 - isvavai.cz</a>
Result on the web
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DOI - Digital Object Identifier
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Alternative languages
Result language
angličtina
Original language name
Adenylate cyclase toxin in virulence of the pertussis agent
Original language description
The capacity of classical Bordetella species to cause respiratory infections in mammals involves the production of an RTX family adenylate cyclase toxin-cytolysin (ACT, AC-Hly, or CyaA). This bifunctional fatty-acylated and T1SS-excreted toxin is a 1706 residue-long fusion of a cytotoxic N-terminal adenylyl cyclase (AC) enzyme (~400 residues) with a prototypic C-terminal Repeat-in-ToXin (RTX) cytolysin (Hly) moiety (~1306 residues). Hly binds the CD11b subunit of the αMβb2 (CD11b/CD18) integrin serving as the complement receptor 3 (CR3) of sentinel myeloid phagocytic cells. Following CD11b binding, CyaA penetrates the plasma membrane of phagocytes, forms small cation-selective pores and delivers the AC enzyme into the cytosol of phagocytes. There, the AC is activated by cytosolic calmodulin and catalyzes unregulated conversion of cellular ATP into cAMP. This hijacks cellular signaling pathways and near-instantly ablates the bactericidal functions of host sentinel phagocytes. I will summarize our studies on the structure-function relationships that underlie CyaA toxin action, such as (i) toxin activation attachment of by fatty-acyl chains, (ii) calcium binding-driven vectorial folding of the RTX domain and (iii) the role of acylated β-hairpins in membrane insertion of CyaA. I will conclude by discussing how the epigenetic reprogramming elicited by CyaA/cAMP signaling in monocytes, suppresses the transcriptional pro-differentiation program of monocytes, to block their transition into bactericidal macrophage cells.
Czech name
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Czech description
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Classification
Type
O - Miscellaneous
CEP classification
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OECD FORD branch
10606 - Microbiology
Result continuities
Project
<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů