Bordetella adenylate cyclase toxin interacts with filamentous haemagglutinin to inhibit biofilm formation in vitro

Casandra Hoffman, Joshua Eby, Mary Gray, F. Heath Damron, Jeffrey Melvin, Peggy Cotter, Erik Hewlett

Research output: Contribution to journalArticle

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Abstract

Bordetella pertussis, the causative agent of whooping cough, secretes and releases adenylate cyclase toxin (ACT), which is a protein bacterial toxin that targets host cells and disarms immune defenses. ACT binds filamentous haemagglutinin (FHA), a surface-displayed adhesin, and until now, the consequences of this interaction were unknown. A B. bronchiseptica mutant lacking ACT produced more biofilm than the parental strain; leading Irie et al. to propose the ACT-FHA interaction could be responsible for biofilm inhibition. Here we characterize the physical interaction of ACT with FHA and provide evidence linking that interaction to inhibition of biofilm in vitro. Exogenous ACT inhibits biofilm formation in a concentration-dependent manner and the N-terminal catalytic domain of ACT (AC domain) is necessary and sufficient for this inhibitory effect. AC Domain interacts with the C-terminal segment of FHA with ∼650 nM affinity. ACT does not inhibit biofilm formation by Bordetella lacking the mature C-terminal domain (MCD), suggesting the direct interaction between AC domain and the MCD is required for the inhibitory effect. Additionally, AC domain disrupts preformed biofilm on abiotic surfaces. The demonstrated inhibition of biofilm formation by a host-directed protein bacterial toxin represents a novel regulatory mechanism and identifies an unprecedented role for ACT.

LanguageEnglish (US)
Pages214-228
Number of pages15
JournalMolecular microbiology
Volume103
Issue number2
DOIs
StatePublished - Jan 1 2017

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Adenylate Cyclase Toxin
Hemagglutinins
Biofilms
Bacterial Toxins
Bordetella
In Vitro Techniques
Bordetella pertussis
Whooping Cough
Catalytic Domain
Proteins

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Hoffman, C., Eby, J., Gray, M., Heath Damron, F., Melvin, J., Cotter, P., & Hewlett, E. (2017). Bordetella adenylate cyclase toxin interacts with filamentous haemagglutinin to inhibit biofilm formation in vitro. Molecular microbiology, 103(2), 214-228. DOI: 10.1111/mmi.13551

Bordetella adenylate cyclase toxin interacts with filamentous haemagglutinin to inhibit biofilm formation in vitro. / Hoffman, Casandra; Eby, Joshua; Gray, Mary; Heath Damron, F.; Melvin, Jeffrey; Cotter, Peggy; Hewlett, Erik.

In: Molecular microbiology, Vol. 103, No. 2, 01.01.2017, p. 214-228.

Research output: Contribution to journalArticle

Hoffman, C, Eby, J, Gray, M, Heath Damron, F, Melvin, J, Cotter, P & Hewlett, E 2017, 'Bordetella adenylate cyclase toxin interacts with filamentous haemagglutinin to inhibit biofilm formation in vitro' Molecular microbiology, vol 103, no. 2, pp. 214-228. DOI: 10.1111/mmi.13551
Hoffman C, Eby J, Gray M, Heath Damron F, Melvin J, Cotter P et al. Bordetella adenylate cyclase toxin interacts with filamentous haemagglutinin to inhibit biofilm formation in vitro. Molecular microbiology. 2017 Jan 1;103(2):214-228. Available from, DOI: 10.1111/mmi.13551
Hoffman, Casandra ; Eby, Joshua ; Gray, Mary ; Heath Damron, F. ; Melvin, Jeffrey ; Cotter, Peggy ; Hewlett, Erik. / Bordetella adenylate cyclase toxin interacts with filamentous haemagglutinin to inhibit biofilm formation in vitro. In: Molecular microbiology. 2017 ; Vol. 103, No. 2. pp. 214-228
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