Translocation and calmodulin-activation of the adenylate cyclase toxin (CyaA) of<i>Bordetella pertussis</i>

Voegele, Alexis; O’Brien, Darragh P.; Subrini, Orso; Sapay, Nicolas; Cannella, Sara; Enguéné, Véronique Yvette Ntsogo; Hessel, Audrey; Karst, Johanna C.; Hourdel, Véronique; Pérez, Ana Cristina Sotomayor; Davi, Marilyne; Veneziano, Rémi; Chopineau, Joël; Vachette, Patrice; Durand, Dominique; Brier, Sébastien; Ladant, Daniel; Chenal, Alexandre

doi:10.1093/femspd/fty085

Cited by 12 publications

(15 citation statements)

References 54 publications

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“…Next, the gene encodes an adenylate cyclase that is a eukaryotic protein activated by calmodulin, to which LanM shows homology. In the case of pathogenic Bordetella pertussis , adenylate cyclase increases cAMP levels in the human host in response to host calmodulin ( Voegele et al, 2018 ). Transcriptional regulators of the MucR family are involved in extracellular polysaccharide synthesis in Rhizobium species (UniProtKB-P55323).…”

Section: Discussionmentioning

confidence: 99%

A Periplasmic Lanthanide Mediator, Lanmodulin, in Methylobacterium aquaticum Strain 22A

Fujitani

Shibata²,

Tani

2022

Front. Microbiol.

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Methylobacterium and Methylorubrum species oxidize methanol via pyrroloquinoline quinone-methanol dehydrogenases (MDHs). MDHs can be classified into two major groups, Ca2+-dependent MDH (MxaF) and lanthanide (Ln3+)-dependent MDH (XoxF), whose expression is regulated by the availability of Ln3+. A set of a siderophore, TonB-dependent receptor, and an ABC transporter that resembles the machinery for iron uptake is involved in the solubilization and transport of Ln3+. The transport of Ln3+ into the cytosol enhances XoxF expression. A unique protein named lanmodulin from Methylorubrum extorquens strain AM1 was identified as a specific Ln3+-binding protein, and its biological function was implicated to be an Ln3+ shuttle in the periplasm. In contrast, it remains unclear how Ln3+ levels in the cells are maintained, because Ln3+ is potentially deleterious to cellular systems due to its strong affinity to phosphate ions. In this study, we investigated the function of a lanmodulin homolog in Methylobacterium aquaticum strain 22A. The expression of a gene encoding lanmodulin (lanM) was induced in response to the presence of La3+. A recombinant LanM underwent conformational change upon La3+ binding. Phenotypic analyses on lanM deletion mutant and overexpressing strains showed that LanM is not necessary for the wild-type and XoxF-dependent mutant’s methylotrophic growth. We found that lanM expression was regulated by MxcQE (a two-component regulator for MxaF) and TonB_Ln (a TonB-dependent receptor for Ln3+). The expression level of mxcQE was altered to be negatively dependent on Ln3+ concentration in ∆lanM, whereas it was constant in the wild type. Furthermore, when exposed to La3+, ∆lanM showed an aggregating phenotype, cell membrane impairment, La deposition in the periplasm evidenced by electron microscopy, differential expression of proteins involved in membrane integrity and phosphate starvation, and possibly lower La content in the membrane vesicle (MV) fractions. Taken together, we concluded that lanmodulin is involved in the complex regulation mechanism of MDHs and homeostasis of cellular Ln levels by facilitating transport and MV-mediated excretion.

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Section: Discussionmentioning

confidence: 99%

A Periplasmic Lanthanide Mediator, Lanmodulin, in Methylobacterium aquaticum Strain 22A

Fujitani

Shibata²,

Tani

2022

Front. Microbiol.

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“…The full activity can be restored by raising the temperature or adding free calcium [13]. The internalization of AC seems to be a monomolecular process, while CyaA channel formation involves more than one CyaA molecule in vivo and in vitro [16,17,32,71,82,83]. A model established by Osickova et al suggests that the water-soluble toxin exists in two conformational isomers [71].…”

Section: Membrane Interaction Of Cyaa: Membrane Binding Adenylate Cyclase (Ac) Translocation and Pore Formationmentioning

confidence: 99%

Membrane Activity and Channel Formation of the Adenylate Cyclase Toxin (CyaA) of Bordetella pertussis in Lipid Bilayer Membranes

Knapp

Benz

2020

Toxins

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The Gram-negative bacterium Bordetella pertussis is the cause of whooping cough. One of its pathogenicity factors is the adenylate cyclase toxin (CyaA) secreted by a Type I export system. The 1706 amino acid long CyaA (177 kDa) belongs to the continuously increasing family of repeat in toxin (RTX) toxins because it contains in its C-terminal half a high number of nine-residue tandem repeats. The protein exhibits cytotoxic and hemolytic activities that target primarily myeloid phagocytic cells expressing the αMβ2 integrin receptor (CD11b/CD18). CyaA represents an exception among RTX cytolysins because the first 400 amino acids from its N-terminal end possess a calmodulin-activated adenylate cyclase (AC) activity. The entry of the AC into target cells is not dependent on the receptor-mediated endocytosis pathway and penetrates directly across the cytoplasmic membrane of a variety of epithelial and immune effector cells. The hemolytic activity of CyaA is rather low, which may have to do with its rather low induced permeability change of target cells and its low conductance in lipid bilayer membranes. CyaA forms highly cation-selective channels in lipid bilayers that show a strong dependence on aqueous pH. The pore-forming activity of CyaA but not its single channel conductance is highly dependent on Ca2+ concentration with a half saturation constant of about 2 to 4 mM.

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“…He also illustrated the use of ACT as a tool for the study of protein-protein interactions [8]. Finally, he presented a model for ACT translocation into target cells and activation of the enzyme by calmodulin [9].…”

Section: Special Session On Adenylate Cyclase Toxinmentioning

confidence: 99%

Highlights of the 12th InternationalBordetellaSymposium

Locht

Carbonetti

Cherry

et al. 2020

Clinical Infectious Diseases

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To commemorate the 100th anniversary of the Nobel prize being awarded to Jules Bordet, the discoverer of Bordetella pertussis, the 12th International Bordetella Symposium was held from 9 to 12 April 2019 at the Université Libre de Bruxelles, where Jules Bordet studied and was Professor of Microbiology. The symposium attracted more than 300 Bordetella experts from 34 countries. They discussed the latest epidemiologic data and clinical aspects of pertussis, Bordetella biology and pathogenesis, immunology and vaccine development, and genomics and evolution. Advanced technological and methodological tools provided novel insights into the genomic diversity of Bordetella and a better understanding of pertussis disease and vaccine performance. New molecular approaches revealed previously unrecognized complexity of virulence gene regulation. Innovative insights into the immune responses to infection by Bordetella resulted in the development of new vaccine candidates. Such discoveries will aid in the design of more effective approaches to control pertussis and other Bordetella-related diseases.

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Translocation and calmodulin-activation of the adenylate cyclase toxin (CyaA) ofBordetella pertussis

Cited by 12 publications

References 54 publications

A Periplasmic Lanthanide Mediator, Lanmodulin, in Methylobacterium aquaticum Strain 22A

A Periplasmic Lanthanide Mediator, Lanmodulin, in Methylobacterium aquaticum Strain 22A

Membrane Activity and Channel Formation of the Adenylate Cyclase Toxin (CyaA) of Bordetella pertussis in Lipid Bilayer Membranes

Highlights of the 12th InternationalBordetellaSymposium

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