Cell wall melanin impedes growth of the Cryptococcus neoformans polysaccharide capsule by sequestering calcium

has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of within the human host, the two most prominent of which are the polysacchari...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2024-09, Vol.121 (38), p.e2412534121
Hauptverfasser: Baker, Rosanna P, Liu, Amy Z, Casadevall, Arturo
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creator Baker, Rosanna P
Liu, Amy Z
Casadevall, Arturo
description has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response.
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subjects Bridge maintenance
Calcium
Calcium - metabolism
Cell culture
Cell Wall - metabolism
Cell walls
Competitive materials
Cryptococcus neoformans
Cryptococcus neoformans - growth & development
Cryptococcus neoformans - metabolism
Fungal Capsules - metabolism
Fungal Polysaccharides - metabolism
Fungi
Humans
Immune response
Immune system
Melanin
Melanins - metabolism
Polysaccharides
Polysaccharides - metabolism
Sequestering
Thickness
Virulence
Virulence factors
title Cell wall melanin impedes growth of the Cryptococcus neoformans polysaccharide capsule by sequestering calcium
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