Research Article

Effect of rapamycin on Cryptococcus neoformans: cellular organization, biophysics and virulence factors

Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

‡Contributed equally to this work

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Vinicius Alves‡

https://orcid.org/0000-0002-8541-3183

Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

‡Contributed equally to this work

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Luiza Pereira

https://orcid.org/0009-0006-4034-255X

Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Bruna Miranda

https://orcid.org/0009-0008-5880-805X

Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Dario Corrêa-Junior

https://orcid.org/0000-0003-2821-4978

Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Maria Helena Galdino Figueiredo-Carvalho

Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

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Marcos Vinicius Santos

Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

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Rodrigo Almeida-Paes

https://orcid.org/0000-0002-6639-6058

Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

Rede Micologia – FAPERJ, Rio de Janeiro, Brazil

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Susana Frases

*Author for correspondence: Tel.: +55 213 938 6564;

E-mail Address: susanafrases@biof.ufrj.br

https://orcid.org/0000-0001-5875-9886

Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Rede Micologia – FAPERJ, Rio de Janeiro, Brazil

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Published Online:18 Sep 2023https://doi.org/10.2217/fmb-2023-0097

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Abstract

Background:Cryptococcus neoformans is an opportunistic fungal pathogen that causes infections mainly in immunosuppressed individuals, such as transplant recipients. Aims: This study investigated the effects of rapamycin, an immunosuppressant drug, on the cellular organization, biophysical characteristics, and main virulence factors of C. neoformans. Methods: Morphological, structural, physicochemical and biophysical analyses of cells and secreted polysaccharides of the reference H99 C. neoformans strain were investigated under the effect of subinhibitory concentrations of rapamycin. Results: Rapamycin at a minimum inhibitory concentration of 2.5 μM reduced C. neoformans cell viability by 53%, decreased capsule, increased cell size, chitin and lipid body formation, and changed peptidase and urease activity. Conclusion: Further studies are needed to assess how rapamycin affects the virulence factors and pathogenicity of C. neoformans.

Plain language summary

Cryptococcosis is a fungal infection caused by a type of fungus called Cryptococcus. Among the Cryptococcus group, Cryptococcus neoformans is often linked to fungal infections in people who have a weak immune system (known as being immunosuppressed). The main aim of this work was to look at the effect of an immunosuppressant called rapamycin, which is commonly used to prevent organ transplant rejection, on the ability of C. neoformans to cause infection. The results showed that this drug stopped the growth of the fungus, dampening its ability to cause disease.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 18, No. 15

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Received 29 April 2023

Accepted 19 July 2023

Published online 18 September 2023

Published in print October 2023

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Author contributions

I Bastos de Andrade, V Alves, Luiza Pereira, B Miranda, MHG Figueiredo-Carvalho, MV Santos: methodology. D Corrêa-Junior, R Almeida-Paes, S Frases: formal analysis. I Bastos de Andrade, V Alves: writing-original draft preparation. I Bastos de Andrade, V Alves, LG, B Miranda, MHG Figueiredo-Carvalho, MV Santos, D Corrêa-Junior, R Almeida-Paes, S Frases: writing-review and editing. R Almeida-Paes, S Frases: funding acquisition.

Financial & competing interests disclosure

This work was supported by the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001- and Fundação de Amparo à Pesquisa do Rio de Janeiro (FAPERJ). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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