Microbial inositol polyphosphate metabolic pathway as drug development target.
Adolfo Saiardi1, Cristina Azevedo1, Yann Desfougères1
1Medical Research Council Laboratory for Molecular Cell Biology, University College London, London, UK.
Advances in Biological Regulation
|October 2, 2017
Summary
Inositol polyphosphates are vital cell messengers, and their synthesis pathways are crucial for organism survival. Targeting inositol kinases in pathogens offers a promising strategy for new antimicrobial therapies.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Inositol polyphosphates (IPs) are essential intracellular messengers regulating diverse cellular functions.
- The synthesis of higher phosphorylated IPs, including IP6, IP7, and IP8, is catalyzed by specific inositol phosphate kinases.
- Disruptions in IP metabolism can lead to severe growth defects or lethality.
Purpose of the Study:
- To explore the significance of inositol polyphosphate metabolic pathways in pathogenic microorganisms.
- To investigate the potential for developing targeted inhibitors against inositol kinases in pathogens.
Main Methods:
- Comparative genomic analysis of inositol phosphate kinase enzymes across eukaryotes.
- Biochemical characterization of inositol phosphate kinase activity.
- Functional studies in pathogenic model organisms like Cryptococcus neoformans and Trypanosome brucei.
Main Results:
- Inositol phosphate kinase sequences show low homology across species, with conserved catalytic residues.
- Highly phosphorylated inositol polyphosphates are critical for the fitness and virulence of pathogens.
- Pathogen inositol kinases represent viable targets for therapeutic intervention.
Conclusions:
- Inositol polyphosphate metabolism is a conserved but divergent pathway across eukaryotes.
- Targeting pathogen-specific inositol kinases presents a promising avenue for novel antimicrobial drug development.
- Further research into these pathways could yield new strategies against infectious diseases.
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