Discovery of fungal surface NADases predominantly present in pathogenic species

Øyvind Strømland, Juha P. Kallio, Annica Pschibul, Renate H. Skoge, Hulda M. Harðardóttir, Lars J. Sverkeli, Thorsten Heinekamp, Olaf Kniemeyer, Marie Migaud, Mikhail V. Makarov, Toni I. Gossmann, Axel A. Brakhage and Mathias Ziegler ()
Additional contact information
Øyvind Strømland: University of Bergen
Juha P. Kallio: University of Bergen
Annica Pschibul: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute
Renate H. Skoge: University of Bergen
Hulda M. Harðardóttir: University of Bergen
Lars J. Sverkeli: University of Bergen
Thorsten Heinekamp: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute
Olaf Kniemeyer: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute
Marie Migaud: University of South Alabama
Mikhail V. Makarov: University of South Alabama
Toni I. Gossmann: Bielefeld University
Axel A. Brakhage: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute
Mathias Ziegler: University of Bergen

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Nicotinamide adenine dinucleotide (NAD) is a key molecule in cellular bioenergetics and signalling. Various bacterial pathogens release NADase enzymes into the host cell that deplete the host’s NAD+ pool, thereby causing rapid cell death. Here, we report the identification of NADases on the surface of fungi such as the pathogen Aspergillus fumigatus and the saprophyte Neurospora crassa. The enzymes harbour a tuberculosis necrotizing toxin (TNT) domain and are predominately present in pathogenic species. The 1.6 Å X-ray structure of the homodimeric A. fumigatus protein reveals unique properties including N-linked glycosylation and a Ca2+-binding site whose occupancy regulates activity. The structure in complex with a substrate analogue suggests a catalytic mechanism that is distinct from those of known NADases, ADP-ribosyl cyclases and transferases. We propose that fungal NADases may convey advantages during interaction with the host or competing microorganisms.

Date: 2021
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DOI: 10.1038/s41467-021-21307-z

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