Number of the records: 1
Cyclic AMP-Elevating Capacity of Adenylate Cyclase Toxin-Hemolysin Is Sufficient for Lung Infection but Not for Full Virulence of Bordetella pertussis
- 1.
SYSNO ASEP 0476224 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Cyclic AMP-Elevating Capacity of Adenylate Cyclase Toxin-Hemolysin Is Sufficient for Lung Infection but Not for Full Virulence of Bordetella pertussis Author(s) 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, ORCIDArticle number e00937-16 Source Title Infection and Immunity. - : American Society for Microbiology - ISSN 0019-9567
Roč. 85, č. 6 (2017), s. 1-22Number of pages 22 s. Language eng - English Country US - United States Keywords Bordetella pertussis ; adenylate cyclase toxin-hemolysin ; cAMP intoxication Subject RIV EE - Microbiology, Virology OECD category Microbiology Subject RIV - cooperation Institute of Molecular Genetics - Microbiology, Virology R&D Projects NV16-28126A GA MZd - Ministry of Health (MZ) GA13-14547S GA ČR - Czech Science Foundation (CSF) GA13-12885S GA ČR - Czech Science Foundation (CSF) GA15-09157S GA ČR - Czech Science Foundation (CSF) GAP302/12/0460 GA ČR - Czech Science Foundation (CSF) LM2015064 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support MBU-M - RVO:61388971 ; UMG-J - RVO:68378050 UT WOS 000405937200012 EID SCOPUS 85019930879 DOI 10.1128/IAI.00937-16 Annotation 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. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2018
Number of the records: 1