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Článek

FT
PubMed

Záznam pochází z PubMed

Pore-forming and enzymatic activities of Bordetella pertussis adenylate cyclase toxin synergize in promoting lysis of monocytes

Infection and immunity. 2006 Apr ; 74 (4) : 2207-14.

Infect Immun
ISSN 0019-9567
Zdroj

Jazyk angličtina Země Spojené státy americké Médium print

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz https://www.medvik.cz/link/pmid16552051

Online Plný text

PubMed 16552051
PubMed Central PMC1418931
DOI 10.1128/iai.74.4.2207-2214.2006
PII: 74/4/2207
Knihovny.cz E-zdroje

MeSH
adenosintrifosfát metabolismus MeSH
adenylátcyklasový toxin toxicita MeSH
AMP cyklický metabolismus MeSH
antigeny CD11b metabolismus MeSH
antigeny CD18 metabolismus MeSH
Bordetella pertussis enzymologie imunologie MeSH
buněčná smrt imunologie MeSH
buněčné linie MeSH
CHO buňky MeSH
Cricetulus MeSH
cytotoxicita imunologická * MeSH
erytrocyty metabolismus MeSH
křečci praví MeSH
monocyty enzymologie imunologie MeSH
myši MeSH
ovce MeSH
permeabilita buněčné membrány imunologie MeSH
zvířata MeSH
Check Tag
křečci praví MeSH
myši MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Názvy látek
adenosintrifosfát MeSH
adenylátcyklasový toxin MeSH
AMP cyklický MeSH
antigeny CD11b MeSH
antigeny CD18 MeSH

Bordetella adenylate cyclase (AC) toxin-hemolysin (CyaA) targets myeloid phagocytes expressing the alphaMbeta2 integrin (CD11b/CD18) and delivers into their cytosol an AC enzyme that converts ATP into cyclic AMP (cAMP). In parallel, CyaA acts as a hemolysin, forming small membrane pores. Using specific mutations, we dissected the contributions of the two activities to cytolytic potency of CyaA on J774A.1 murine monocytes. The capacity of AC to penetrate cells and deplete cytosolic ATP was essential for promoting lysis and the enzymatically inactive but fully hemolytic CyaA-AC- toxoid exhibited a 15-fold-lower cytolytic capacity on J774A.1 cells than intact CyaA. Moreover, a two- or fourfold drop of specific hemolytic activity of the CyaA-E570Q and CyaA-E581P mutants was overpowered by an intact capacity to dissipate cytosolic ATP into cAMP, allowing the less hemolytic proteins to promote lysis of J774A.1 cells as efficiently as intact CyaA. However, an increased hemolytic activity, due to lysine substitutions of glutamates 509, 516, and 581 in the pore-forming domain, conferred on AC- toxoids a correspondingly enhanced cytolytic potency. Moreover, a threefold increase in hemolytic activity could override a fourfold drop in capacity to convert cellular ATP to cAMP, conferring on the CyaA-E581K construct an overall twofold increased cytolytic potency. Hence, although appearing auxiliary in cytolytic action of the toxin on nucleated cells, the pore-forming activity can synergize with ATP-depleting activity of the cell-invasive AC enzyme and complement its action toward maximal cytotoxicity.

Institute of Microbiology CAS Videnska 1083 CZ 142 20 Prague 4 Czech Republic

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