Počet záznamů: 1

Cyclic AMP-Elevating Capacity of Adenylate Cyclase Toxin-Hemolysin Is Sufficient for Lung Infection but Not for Full Virulence of Bordetella pertussis

SYSNO ASEP	0476224
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Cyclic AMP-Elevating Capacity of Adenylate Cyclase Toxin-Hemolysin Is Sufficient for Lung Infection but Not for Full Virulence of Bordetella pertussis
Tvůrce(i)	Škopová, Karolína (MBU-M) Tomalová, Barbora (MBU-M)_ORCID Kanchev, Ivan (UMG-J)_RID Rossmann, Pavel (MBU-M) Švédová, Martina (MBU-M) Adkins, Irena (MBU-M) Bíbová, Ilona (MBU-M)_RID Tomala, Jakub (MBU-M)_{RID, ORCID} Mašín, Jiří (MBU-M)_{RID, ORCID} Guiso, N. (FR) Osička, Radim (MBU-M)_{RID, ORCID} Sedláček, Radislav (UMG-J)_RID Kovář, Marek (MBU-M)_{RID, ORCID} Šebo, Peter (MBU-M)_{RID, ORCID}
Číslo článku	e00937-16
Zdroj.dok.	Infection and Immunity. - : American Society for Microbiology - ISSN 0019-9567 Roč. 85, č. 6 (2017), s. 1-22
Poč.str.	22 s.
Jazyk dok.	eng - angličtina
Země vyd.	US - Spojené státy americké
Klíč. slova	Bordetella pertussis ; adenylate cyclase toxin-hemolysin ; cAMP intoxication
Vědní obor RIV	EE - Mikrobiologie, virologie
Obor OECD	Microbiology
Vědní obor RIV – spolupráce	Ústav molekulární genetiky - Mikrobiologie, virologie
CEP	NV16-28126A GA MZd - Ministerstvo zdravotnictví
	GA13-14547S GA ČR - Grantová agentura ČR
	GA13-12885S GA ČR - Grantová agentura ČR
	GA15-09157S GA ČR - Grantová agentura ČR
	GAP302/12/0460 GA ČR - Grantová agentura ČR
	LM2015064 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
	LM2015040 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
Institucionální podpora	MBU-M - RVO:61388971 ; UMG-J - RVO:68378050
UT WOS	000405937200012
EID SCOPUS	85019930879
DOI	10.1128/IAI.00937-16
Anotace	The adenylate cyclase toxin-hemolysin (CyaA, ACT, or AC-Hly) of Bordetella pertussis targets phagocytic cells expressing the complement receptor 3 (CR3, Mac-1, αMbeta2 integrin, or CD11b/CD18). CyaA delivers into cells an N-terminal adenylyl cyclase (AC) enzyme domain that is activated by cytosolic calmodulin and catalyzes unregulated conversion of cellular ATP into cyclic AMP (cAMP), a key second messenger subverting bactericidal activities of phagocytes. In parallel, the hemolysin (Hly) moiety of CyaA forms cation-selective hemolytic pores that permeabilize target cell membranes. We constructed the first B. pertussis mutant secreting a CyaA toxin having an intact capacity to deliver the AC enzyme into CD11b-expressing (CD11b+) host phagocytes but impaired in formation of cell-permeabilizing pores and defective in cAMP elevation in CD11b- cells. The nonhemolytic AC+ Hly- bacteria inhibited the antigen-presenting capacities of coincubated mouse dendritic cells in vitro and skewed their Toll-like receptor (TLR)-triggered maturation toward a tolerogenic phenotype. The AC+ Hly- mutant also infected mouse lungs as efficiently as the parental AC+ Hly+ strain. Hence, elevation of cAMP in CD11b- cells and/or the pore-forming capacity of CyaA were not required for infection of mouse airways. The latter activities were, however, involved in bacterial penetration across the epithelial layer, enhanced neutrophil influx into lung parenchyma during sublethal infections, and the exacerbated lung pathology and lethality of B. pertussis infections at higher inoculation doses (more than 107 CFU/mouse). The pore-forming activity of CyaA further synergized with the cAMP-elevating activity in downregulation of major histocompatibility complex class II (MHC-II) molecules on infiltrating myeloid cells, likely contributing to immune subversion of host defenses by the whooping cough agent.
Pracoviště	Mikrobiologický ústav
Kontakt	Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
Rok sběru	2018

Počet záznamů: 1