Structure–Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes

Novak, Jakub; Cerny, Ondrej; Osickova, Adriana; Linhartova, Irena; Masin, Jiri; Bumba, Ladislav; Sebo, Peter; Osicka, Radim

doi:10.3390/toxins9100300

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Structure–Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes

by

Jakub Novak

^1,2,

Ondrej Cerny

^1,†

,

Adriana Osickova

^1,2,

Irena Linhartova

¹,

Jiri Masin

¹,

Ladislav Bumba

¹

,

Peter Sebo

¹ and

Radim Osicka

^1,*

¹

Institute of Microbiology of the CAS, v.v.i., 142 20 Prague, Czech Republic

²

Faculty of Science, Charles University in Prague, 128 43 Prague, Czech Republic

^*

Author to whom correspondence should be addressed.

^†

Present address: MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK

Toxins 2017, 9(10), 300; https://doi.org/10.3390/toxins9100300

Submission received: 29 August 2017 / Revised: 19 September 2017 / Accepted: 21 September 2017 / Published: 24 September 2017

(This article belongs to the Special Issue Adenylate Cyclase (CyaA) Toxin)

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Abstract

Bordetellae, pathogenic to mammals, produce an immunomodulatory adenylate cyclase toxin–hemolysin (CyaA, ACT or AC-Hly) that enables them to overcome the innate immune defense of the host. CyaA subverts host phagocytic cells by an orchestrated action of its functional domains, where an extremely catalytically active adenylyl cyclase enzyme is delivered into phagocyte cytosol by a pore-forming repeat-in-toxin (RTX) cytolysin moiety. By targeting sentinel cells expressing the complement receptor 3, known as the CD11b/CD18 (α_Mβ₂) integrin, CyaA compromises the bactericidal functions of host phagocytes and supports infection of host airways by Bordetellae. Here, we review the state of knowledge on structural and functional aspects of CyaA toxin action, placing particular emphasis on signaling mechanisms by which the toxin-produced 3′,5′-cyclic adenosine monophosphate (cAMP) subverts the physiology of phagocytic cells.

Keywords: adenylate cyclase toxin; Bordetella; β₂ integrins; cAMP; CD11b/CD18; cell signaling; complement receptor 3; innate immunity; membrane pores; repeats-in-toxin

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MDPI and ACS Style

Novak, J.; Cerny, O.; Osickova, A.; Linhartova, I.; Masin, J.; Bumba, L.; Sebo, P.; Osicka, R. Structure–Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes. Toxins 2017, 9, 300. https://doi.org/10.3390/toxins9100300

AMA Style

Novak J, Cerny O, Osickova A, Linhartova I, Masin J, Bumba L, Sebo P, Osicka R. Structure–Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes. Toxins. 2017; 9(10):300. https://doi.org/10.3390/toxins9100300

Chicago/Turabian Style

Novak, Jakub, Ondrej Cerny, Adriana Osickova, Irena Linhartova, Jiri Masin, Ladislav Bumba, Peter Sebo, and Radim Osicka. 2017. "Structure–Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes" Toxins 9, no. 10: 300. https://doi.org/10.3390/toxins9100300

APA Style

Novak, J., Cerny, O., Osickova, A., Linhartova, I., Masin, J., Bumba, L., Sebo, P., & Osicka, R. (2017). Structure–Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes. Toxins, 9(10), 300. https://doi.org/10.3390/toxins9100300

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Structure–Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes

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