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Interactions between copper homeostasis and the fungal cell wall affect copper stress resistance.

Publication ,  Journal Article
Probst, C; Garcia-Santamarina, S; Brooks, JT; Van Der Kloet, I; Baars, O; Ralle, M; Thiele, DJ; Alspaugh, JA
Published in: PLoS Pathog
June 2022

Copper homeostasis mechanisms are essential for microbial adaption to changing copper levels within the host during infection. In the opportunistic fungal pathogen Cryptococcus neoformans (Cn), the Cn Cbi1/Bim1 protein is a newly identified copper binding and release protein that is highly induced during copper limitation. Recent studies demonstrated that Cbi1 functions in copper uptake through the Ctr1 copper transporter during copper limitation. However, the mechanism of Cbi1 action is unknown. The fungal cell wall is a dynamic structure primarily composed of carbohydrate polymers, such as chitin and chitosan, polymers known to strongly bind copper ions. We demonstrated that Cbi1 depletion affects cell wall integrity and architecture, connecting copper homeostasis with adaptive changes within the fungal cell wall. The cbi1Δ mutant strain possesses an aberrant cell wall gene transcriptional signature as well as defects in chitin / chitosan deposition and exposure. Furthermore, using Cn strains defective in chitosan biosynthesis, we demonstrated that cell wall chitosan modulates the ability of the fungal cell to withstand copper stress. Given the previously described role for Cbi1 in copper uptake, we propose that this copper-binding protein could be involved in shuttling copper from the cell wall to the copper transporter Ctr1 for regulated microbial copper uptake.

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Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

June 2022

Volume

18

Issue

6

Start / End Page

e1010195

Location

United States

Related Subject Headings

  • Virology
  • Homeostasis
  • Gene Expression Regulation, Fungal
  • Fungal Proteins
  • Cryptococcus neoformans
  • Cryptococcosis
  • Copper Transport Proteins
  • Copper
  • Chitosan
  • Chitin
 

Citation

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Probst, C., Garcia-Santamarina, S., Brooks, J. T., Van Der Kloet, I., Baars, O., Ralle, M., … Alspaugh, J. A. (2022). Interactions between copper homeostasis and the fungal cell wall affect copper stress resistance. PLoS Pathog, 18(6), e1010195. https://doi.org/10.1371/journal.ppat.1010195
Probst, Corinna, Sarela Garcia-Santamarina, Jacob T. Brooks, Inge Van Der Kloet, Oliver Baars, Martina Ralle, Dennis J. Thiele, and J Andrew Alspaugh. “Interactions between copper homeostasis and the fungal cell wall affect copper stress resistance.PLoS Pathog 18, no. 6 (June 2022): e1010195. https://doi.org/10.1371/journal.ppat.1010195.
Probst C, Garcia-Santamarina S, Brooks JT, Van Der Kloet I, Baars O, Ralle M, et al. Interactions between copper homeostasis and the fungal cell wall affect copper stress resistance. PLoS Pathog. 2022 Jun;18(6):e1010195.
Probst, Corinna, et al. “Interactions between copper homeostasis and the fungal cell wall affect copper stress resistance.PLoS Pathog, vol. 18, no. 6, June 2022, p. e1010195. Pubmed, doi:10.1371/journal.ppat.1010195.
Probst C, Garcia-Santamarina S, Brooks JT, Van Der Kloet I, Baars O, Ralle M, Thiele DJ, Alspaugh JA. Interactions between copper homeostasis and the fungal cell wall affect copper stress resistance. PLoS Pathog. 2022 Jun;18(6):e1010195.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

June 2022

Volume

18

Issue

6

Start / End Page

e1010195

Location

United States

Related Subject Headings

  • Virology
  • Homeostasis
  • Gene Expression Regulation, Fungal
  • Fungal Proteins
  • Cryptococcus neoformans
  • Cryptococcosis
  • Copper Transport Proteins
  • Copper
  • Chitosan
  • Chitin