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Cgm1 is a β-galactoside α-(1 → 4)-mannosyltransferase involved in the biosynthesis of capsular glucuronoxylomannogalactan in Cryptococcus neoformans

Summary

Researchers identified a new fungal enzyme called Cgm1 that helps the fungus Cryptococcus neoformans build its protective capsule, which allows it to evade the immune system. When this enzyme is disabled, the fungus becomes weak at body temperature and triggers a stronger immune response in infected mice. Since humans and plants don’t have this enzyme, it could be a promising target for developing new antifungal medications.

Background

Cryptococcus neoformans is a major pathogenic yeast causing cryptococcosis with high mortality rates. The fungal capsule consists of glucuronoxylomannan and glucuronoxylomannogalactan, which are virulence factors enabling immune evasion. Understanding the enzymes involved in capsular polysaccharide biosynthesis is important for developing antifungal therapies.

Objective

This study aimed to identify novel glycosyltransferases involved in glucuronoxylomannogalactan biosynthesis. The research focused on characterizing enzymes responsible for synthesizing the galactomannan side chain, which contains a unique α-mannose residue attached to β-galactose not found in other organisms.

Results

Two novel β-galactoside α-(1 → 4)-mannosyltransferases designated Cgm1 and Cgm2 were identified and classified as a new GT139 family. Cgm1 (also called Goe1) catalyzes the addition of α-mannose to the C-4 position of β-galactose. The cgm1 disruptant exhibited temperature sensitivity at 37°C, nearly complete loss of the galactomannan side chain, and significantly elevated interferon-γ production in infected mice.

Conclusion

Cgm1 is the primary α-(1 → 4)-mannosyltransferase responsible for galactomannan side chain biosynthesis in glucuronoxylomannogalactan and plays crucial roles in temperature tolerance and immune evasion. Cgm1 homologs are absent in mammals and plants, making them promising targets for antifungal drug development.
  • Published in:Journal of Biological Chemistry,
  • Study Type:Experimental Research,
  • Source: PMC12493134, PMID: 40876590
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