Biofilm production by the multidrug-resistant fungus <i>Candida haemulonii</i> is affected by aspartic peptidase inhibitor

Joice Cavalcanti Lima; Lívia de Souza Ramos; Pedro Fernandes Barbosa; Iuri Casemiro Barcellos; Marta Helena Branquinha; André Luis Souza dos Santos; Joice Cavalcanti Lima; Lívia de Souza Ramos; Pedro Fernandes Barbosa; Iuri Casemiro Barcellos; Marta Helena Branquinha; André Luis Souza dos Santos

doi:10.3934/microbiol.2025012

AIMS Microbiology

2025, Volume 11, Issue 1: 228-241. doi: 10.3934/microbiol.2025012

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Research article Special Issues

Biofilm production by the multidrug-resistant fungus Candida haemulonii is affected by aspartic peptidase inhibitor

Joice Cavalcanti Lima ^1,2,
Lívia de Souza Ramos ¹,
Pedro Fernandes Barbosa ^1,2,3,
Iuri Casemiro Barcellos ^1,4,
Marta Helena Branquinha ^1,2,5,
André Luis Souza dos Santos ^{1,2,3,5
,
,}

1.
Laboratório de Estudos Avançados em Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
2.
Programa de Pós-Graduação em Ciências (Microbiologia), Instituto de Microbiologia Paulo de Góes (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
3.
Programa de Pós-Graduação em Bioquímica (PPGBq), Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
4.
Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro (IFRJ), Rio de Janeiro, RJ, Brazil
5.
Rede Micologia RJ – Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro, RJ, Brazil

Received: 02 December 2024 Revised: 13 March 2025 Accepted: 14 March 2025 Published: 21 March 2025

Candida haemulonii is an emerging, opportunistic, and multidrug-resistant fungal pathogen. Recently, our group reported the ability of C. haemulonii to form biofilm and secrete aspartic-type peptidases (Saps). Herein, we investigated the correlation between Saps production and biofilm formation along C. haemulonii growth in yeast carbon base medium supplemented with albumin (a Sap-inducing condition) and in the presence of the classical Sap inhibitor pepstatin A. Under these conditions, the biofilm biomass increased on a polystyrene surface, reaching its maximum at 96 h, while maximum biofilm viability was detected at 48 h. The release of Saps during biofilm formation showed an inverse trend, with the highest enzymatic activity measured after 24 h. In the presence of pepstatin A, a significant reduction in biofilm parameters (biomass and viability), as well as in albumin consumption by biofilm-forming cells was detected. These findings underscore the importance of Saps during the biofilm development in C. haemulonii.
- Candida haemulonii,
- biofilm,
- secreted aspartic peptidases,
- aspartic peptidase inhibitor,
- pepstatin A,
- HIV peptidase inhibitors
Citation: Joice Cavalcanti Lima, Lívia de Souza Ramos, Pedro Fernandes Barbosa, Iuri Casemiro Barcellos, Marta Helena Branquinha, André Luis Souza dos Santos. Biofilm production by the multidrug-resistant fungus Candida haemulonii is affected by aspartic peptidase inhibitor[J]. AIMS Microbiology, 2025, 11(1): 228-241. doi: 10.3934/microbiol.2025012

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Abstract

Candida haemulonii is an emerging, opportunistic, and multidrug-resistant fungal pathogen. Recently, our group reported the ability of C. haemulonii to form biofilm and secrete aspartic-type peptidases (Saps). Herein, we investigated the correlation between Saps production and biofilm formation along C. haemulonii growth in yeast carbon base medium supplemented with albumin (a Sap-inducing condition) and in the presence of the classical Sap inhibitor pepstatin A. Under these conditions, the biofilm biomass increased on a polystyrene surface, reaching its maximum at 96 h, while maximum biofilm viability was detected at 48 h. The release of Saps during biofilm formation showed an inverse trend, with the highest enzymatic activity measured after 24 h. In the presence of pepstatin A, a significant reduction in biofilm parameters (biomass and viability), as well as in albumin consumption by biofilm-forming cells was detected. These findings underscore the importance of Saps during the biofilm development in C. haemulonii.

Abbreviations

APV

Amprenavir

BHI

Brain Heart Infusion

BSA

Bovine Serum Albumin

DNV

Darunavir

E-64

trans-Epoxysuccinyl-L-Leucylamido-(4-Guanidino)-Butane

HIV

Human Immunodeficiency Virus

LPV

Lopinavir

NFV

Nelfinavir

PBS

Phosphate-Buffered Saline

PHEN

1,10-Phenanthroline

PMSF

Phenylmethylsulfonyl Fluoride

RPMI

Roswell Park Memorial Institute

RTV

Ritonavir

SAPs

Secreted Aspartic Peptidases

SDS-PAGE

Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis

XTT

2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (Tetrazolium Salt)

YCB

Yeast Carbon Base

YPD

Yeast Extract-Peptone-Dextrose

Acknowledgments

This study was supported by grants from the Brazilian Agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa no Estado do Rio de Janeiro (FAPERJ) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES–Financial code 001).

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection, analysis, visualization, and data curation were performed by Joice Lima, Lívia Ramos, Pedro Barbosa and Iuri Barcellos The first draft of the manuscript was written by Joice Lima and Pedro Barbosa and André Santos reviewed the previous versions of the manuscript. All authors read and approved the final manuscript.

Competing interests

The authors declare no competing interest.

References

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