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About the Authors:
Stefan Kunz
Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Resources, Visualization, Writing - original draft, Writing - review & editing
* E-mail: [email protected]
Affiliations Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland, Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute of Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
ORCID http://orcid.org/0000-0003-1691-503X
Vreni Balmer
Roles Investigation
Affiliation: Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
Geert Jan Sterk
Roles Resources, Writing - review & editing
Affiliation: Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute of Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Michael P. Pollastri
Roles Resources, Writing - review & editing
Affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, United States of America
Rob Leurs
Roles Funding acquisition, Resources, Writing - review & editing
Affiliation: Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute of Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Norbert Müller
Roles Funding acquisition, Resources, Writing - original draft, Writing - review & editing
Affiliation: Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
Andrew Hemphill
Roles Conceptualization, Funding acquisition, Resources, Writing - original draft, Writing - review & editing
Affiliation: Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
Cornelia Spycher
Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Resources, Visualization, Writing - original draft, Writing - review & editing
Current address: Euresearch, Head Office Bern, Bern, Switzerland
Affiliation: Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, SwitzerlandAbstract
Background
Giardiasis is an intestinal infection correlated with poverty and poor drinking water quality, and treatment options are limited. According to the Center for Disease Control and Prevention, Giardia infections afflict nearly 33% of people in developing countries, and 2% of the adult population in the developed world. This study describes the single cyclic nucleotide-specific phosphodiesterase (PDE) of G. lamblia and assesses PDE inhibitors as a new generation of anti-giardial drugs.
Methods
An extensive search of the Giardia genome database identified a single gene coding for a class I PDE, GlPDE. The predicted protein sequence was analyzed in-silico to characterize its domain structure and catalytic domain. Enzymatic activity of GlPDE was established by complementation of a PDE-deficient Saccharomyces...