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Antifungal activity of a trypsin inhibitor from Salvia hispanica L. (chia) seeds against fluconazole-resistant strains of Candida spp. and evaluation of its toxicity in vitro

  • Biotechnology and Industrial Microbiology - Research Paper
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Abstract

The incidence of Candida species resistant to traditional antifungal drugs is increasing globally. This issue significantly impacts patients' lives and increases healthcare expenses, confirming the need to develop novel therapeutic strategies. Recently, a thermostable trypsin inhibitor named ShTI (11.558 kDa), which has antibacterial effects on Staphylococcus aureus, was isolated from Salvia hispanica L. (chia) seeds. This study aimed to assess the antifungal effect of ShTI against Candida species and its synergism with fluconazole and to evaluate its mode of action. Preliminary toxicological studies on mouse fibroblasts were also performed. ShTI exhibited antifungal effects against C. parapsilosis (ATCC® 22,019), C. krusei (ATCC® 6258), and six clinical fluconazole-resistant strains of C. albicans (2), C. parapsilosis (2), and C. tropicalis (2). The minimum inhibitory concentration (MIC) values were 4.1 µM (inhibiting 50% of the isolates) and 8.2 µM (inhibiting 100% of the isolates). Additionally, when combined with fluconazole, ShTI had a synergistic effect on C. albicans, altering the morphological structure of the yeast. The mode of action of ShTI against C. krusei (ATCC® 6258) and C. albicans involves cell membrane permeabilization, the overproduction of reactive oxygen species, the formation of pseudohyphae, pore formation, and consequently, cell death. In addition, ShTI (8.65 and 17.3 µM) had noncytotoxic and nongenotoxic effects on L929 mouse fibroblasts. These findings suggest that ShTI could be a promising antimicrobial candidate, but further research is necessary to advance its application as a novel antifungal agent.

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Funding

The authors would like to thank the Brazilian institution CAPES (Coordination for the Improvement of Higher Education Personnel) for the grant (scholarship) and the Drug Research and Development Center—Federal University of Ceará (NPDM-UFC) for the infrastructure and support. The authors would like to thank the Central Analítica-UFC/CT-INFRA/MCTI-SISANO/Pró-Equipamentos CAPES for analysis by scanning electron microscopy (SEM). The authors received no financial support for the research, authorship, and/or publication of this article.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Science Center, Federal University of Ceará, Campus Do Pici Prof. Prisco Bezerra, Fortaleza, CE, 60440-900, Brazil

    Francisca Cristiane Nogueira, Adson Ávila de Souza, Nadine Monteiro Salgueiro Araújo, Larissa Alves Lopes de Souza, Daniele de Oliveira Bezerra de Sousa & Hermógenes David de Oliveira

  2. Department of Biology, Science Center, Federal University of Ceará, Campus Do Pici Prof. Prisco Bezerra, Fortaleza, CE, 60440-900, Brazil

    Rafael Guimarães Gomes Silva

  3. Drug Research and Development Center, Federal University of Ceará, Campus Do Porangabussu, Fortaleza, CE, 60430-270, Brazil

    Bruno Coêlho Cavalcanti, Manoel Odorico de Moraes Filho, Lívia Gurgel do Amaral Valente Sá & Hélio Vitoriano Nobre Júnior

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Contributions

Francisca Cristiane Nogueira: conceptualization, methodology design, validation, investigation, data curation, formal analysis, writing—original draft and writing—review and editing. Adson Ávila de Souza: investigation and writing—review and editing. Nadine Monteiro Salgueiro Araújo: investigation and formal analysis. Larissa Alves Lopes de Souza: investigation. Rafael Guimarães Gomes Silva: investigation. Daniele de Oliveira Bezerra de Sousa: methodology design, validation, investigation, formal analysis from antifungal assays. Bruno Cêlho Calvalcanti: methodology design, validation, investigation, data curation, formal analysis from toxicology assays. Manoel Odorico de Moraes Filho: methodology design, validation, investigation, data curation, formal analysis from toxicology assays. Lívia Gurgel do Amaral Valente Sá: investigation and formal analysis from antifungal assays. Hélio Vitoriano Nobre Júnior: methodology design, investigation, formal analysis from antifungal assays. Hermógenes David de Oliveira: conceptualization, formal analysis, data curation, supervision, funding acquisition, writing—review and editing.

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Nogueira, F.C., de Souza, A.Á., Araújo, N.M.S. et al. Antifungal activity of a trypsin inhibitor from Salvia hispanica L. (chia) seeds against fluconazole-resistant strains of Candida spp. and evaluation of its toxicity in vitro. Braz J Microbiol 55, 1205–1217 (2024). https://doi.org/10.1007/s42770-024-01337-7

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