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Phosphoglucose isomerase is important for Aspergillus fumigatuscell wall biogenesis

DOI: 10.1128/mbio.01426-22 DOI Help

Authors: Yao Zhou (Guangxi Academy of Sciences; Guangxi University) , Kaizhou Yan (University of Dundee) , Qijian Qin (Guangxi Academy of Sciences) , Olawale G. Raimi (University of Dundee) , Chao Du (Guangxi Academy of Sciences; Guangxi University) , Bin Wang (Guangxi Academy of Sciences) , Chukwuemeka Samson Ahamefule (Guangxi Academy of Sciences) , Bartosz Kowalski (University of Dundee) , Cheng Jin (Guangxi Academy of Sciences; State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences) , Daniel M. F. Van Aalten (University of Dundee) , Wenxia Fang (Guangxi Academy of Sciences; Guangxi University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Mbio , VOL 228

State: Published (Approved)
Published: August 2022
Diamond Proposal Number(s): 26793

Open Access Open Access

Abstract: Aspergillus fumigatus is a devastating opportunistic fungal pathogen causing hundreds of thousands of deaths every year. Phosphoglucose isomerase (PGI) is a glycolytic enzyme that converts glucose-6-phosphate to fructose-6-phosphate, a key precursor of fungal cell wall biosynthesis. Here, we demonstrate that the growth of A. fumigatus is repressed by the deletion of pgi, which can be rescued by glucose and fructose supplementation in a 1:10 ratio. Even under these optimized growth conditions, the Δpgi mutant exhibits severe cell wall defects, retarded development, and attenuated virulence in Caenorhabditis elegans and Galleria mellonella infection models. To facilitate exploitation of A. fumigatus PGI as an antifungal target, we determined its crystal structure, revealing potential avenues for developing inhibitors, which could potentially be used as adjunctive therapy in combination with other systemic antifungals.

Diamond Keywords: Fungi; Enzymes

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography

Other Facilities: ID23-1 at ESRF

Added On: 08/08/2022 08:52

Documents:
mbio.01426-22.pdf

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)