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Bordetella Adenylate Cyclase Toxin Elicits Airway Mucin Secretion through Activation of the cAMP Response Element Binding Protein

SYSNO ASEP	0547494
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Bordetella Adenylate Cyclase Toxin Elicits Airway Mucin Secretion through Activation of the cAMP Response Element Binding Protein
Author(s)	Malandra, Anna (MBU-M)_ORCID Rahman, Waheed Ur (MBU-M)_ORCID Klímová, Nela (MBU-M)_ORCID Streparola, Gaia (MBU-M) Holubová, Jana (MBU-M)_{RID, ORCID} Osičková, Adriana (MBU-M)_{RID, ORCID} Bariselli, S. (IT) Šebo, Peter (MBU-M)_{RID, ORCID} Osička, Radim (MBU-M)_{RID, ORCID}
Article number	9064
Source Title	International Journal of Molecular Sciences. - : MDPI Roč. 22, č. 16 (2021)
Number of pages	16 s.
Language	eng - English
Country	CH - Switzerland
Keywords	adenylate cyclase toxin ; Bordetella ; cAMP ; creb ; epithelium ; mucin ; pertussis toxin
Subject RIV	EE - Microbiology, Virology
OECD category	Microbiology
R&D Projects	GA19-12695S GA ČR - Czech Science Foundation (CSF)
	GX19-27630X GA ČR - Czech Science Foundation (CSF)
	LM2018133 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	EF18_046/0015861 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Research Infrastructure	CCP II - 90126 - Ústav molekulární genetiky AV ČR, v. v. i.
Method of publishing	Open access
Institutional support	MBU-M - RVO:61388971
UT WOS	000689237100001
EID SCOPUS	85113730131
DOI	10.3390/ijms22169064
Annotation	The mucus layer protects airway epithelia from damage by noxious agents. Intriguingly, Bordetella pertussis bacteria provoke massive mucus production by nasopharyngeal epithelia during the initial coryza-like catarrhal stage of human pertussis and the pathogen transmits in mucus-containing aerosol droplets expelled by sneezing and post-nasal drip-triggered cough. We investigated the role of the cAMP-elevating adenylate cyclase (CyaA) and pertussis (PT) toxins in the upregulation of mucin production in B. pertussis-infected airway epithelia. Using human pseudostratified airway epithelial cell layers cultured at air-liquid interface (ALI), we show that purified CyaA and PT toxins (100 ng/mL) can trigger production of the major airway mucins Muc5AC and Muc5B. Upregulation of mucin secretion involved activation of the cAMP response element binding protein (CREB) and was blocked by the 666-15-Calbiochem inhibitor of CREB-mediated gene transcription. Intriguingly, a B. pertussis mutant strain secreting only active PT and producing the enzymatically inactive CyaA-AC(-) toxoid failed to trigger any important mucus production in infected epithelial cell layers in vitro or in vivo in the tracheal epithelia of intranasally infected mice. In contrast, the PT- toxoid-producing B. pertussis mutant secreting the active CyaA toxin elicited a comparable mucin production as infection of epithelial cell layers or tracheal epithelia of infected mice by the wild-type B. pertussis secreting both PT and CyaA toxins. Hence, the cAMP-elevating activity of B. pertussis-secreted CyaA was alone sufficient for activation of mucin production through a CREB-dependent mechanism in B. pertussis-infected airway epithelia in vivo.
Workplace	Institute of Microbiology
Contact	Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
Year of Publishing	2022
Electronic address	https://www.mdpi.com/1422-0067/22/16/9064

Number of the records: 1