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Chia (Salvia hispanica L.) Seeds Contain a Highly Stable Trypsin Inhibitor with Potential for Bacterial Management Alone or in Drug Combination Therapy with Oxacillin

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Abstract

The emergence of antibiotic resistance poses a serious and challenging threat to healthcare systems, making it imperative to discover novel therapeutic options. This work reports the isolation and characterization of a thermostable trypsin inhibitor from chia (Salvia hispanica L.) seeds, with antibacterial activity against Staphylococcus aureus sensitive and resistant to methicillin. The trypsin inhibitor ShTI was purified from chia seeds through crude extract heat treatment, followed by affinity and reversed-phase chromatography. Tricine-SDS–PAGE revealed a single glycoprotein band of ~ 11 kDa under nonreducing conditions, confirmed by mass spectrometry analysis (11.558 kDa). ShTI was remarkably stable under high temperatures (100 °C; 120 min) and a broad pH range (2–10; 30 min). Upon exposure to DTT (0.1 M; 120 min), ShTI antitrypsin activity was partially lost (~ 38%), indicating the participation of disulfide bridges in its structure. ShTI is a competitive inhibitor (Ki = 1.79 × 10–8 M; IC50 = 1.74 × 10–8 M) that forms a 1:1 stoichiometry ratio for the ShTI:trypsin complex. ShTI displayed antibacterial activity alone (MICs range from 15.83 to 19.03 µM) and in combination with oxacillin (FICI range from 0.20 to 0.33) against strains of S. aureus, including methicillin-resistant strains. Overproduction of reactive oxygen species and plasma membrane pore formation are involved in the antibacterial action mode of ShTI. Overall, ShTI represents a novel candidate for use as a therapeutic agent for the bacterial management of S. aureus infections.

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Data Availability

All data generated or analyzed during this study are available from the corresponding author upon reasonable request.

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Funding

The authors thank the Brazilian institutions CNPq (National Council for Scientific and Technological Development – Award number: 431827/2016–8), CAPES (Coordination of Improvement of Higher Education, and Drug Research and Development Center—Federal University of Ceará (NPDM-UFC) for physical installation and financial support of this research. We also gratefully acknowledge the Center of Advanced Microscopy and Microanalysis (Central Analytical Facility) at the Federal University of Ceará, Brazil, for the scanning electron microscopy (SEM) analysis.

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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

    Adson Ávila de Souza, Adrianne Maia Lima, Daniele dede Oliveira BezerraSousa, Francisca Cristiane Nogueira, José Carlos do Sacramento Neto, Lucas Pinheiro Dias, Nadine Monteiro Salgueiro Araújo & Hermógenes David de Oliveira

  2. Department of Fisher Engineering, Center of Agricultural Sciences, Federal University of Ceará, Campus do Pici Prof. Prisco Bezerra, Fortaleza, CE, 60455-970, Brazil

    Celso Shiniti Nagano

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

    Hélio Vitoriano Nobre Júnior, Cecília Rocha da Silva, Lívia Gurgel do Amaral Valente Sá, João Batista de Andrade Neto, Fátima Daiana Dias Barroso & Maria Elisabete Amaral de Moraes

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  1. Adson Ávila de Souza
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Contributions

Adson Ávila de Souza: conceptualization, methodology design, validation, investigation, data curation, formal analysis, writing—original draft and writing—review and editing. Adrianne Maia Lima: investigation. Daniele de Oliveira Bezerra de Sousa: funding acquisition, writing—initial draft and writing—review and editing. Francisca Cristiane Nogueira: investigation. José Carlos do Sacramento Neto: investigation. Lucas Pinheiro Dias: research and formal analysis. Nadine Monteiro Salgueiro Araújo: investigation and formal analysis. Celso Shiniti Nagano: investigation, formal analysis, funding acquisition, writing—original draft and writing—review and editing. Hélio Vitoriano Nobre Júnior: funding acquisition, writing—initial draft and writing—review and editing. Cecília Rocha da Silva: funding acquisition, writing—original draft and writing—review and editing. Lívia Gurgel do Amaral Valente Sá: investigation and formal analysis. João Batista de Andrade Neto: writing—initial draft and writing—review and editing. Fátima Daiana Dias Barroso: investigation and formal analysis. Maria Elisabete Amaral de Moraes: funding acquisition, writing—original draft and writing—review and editing. Hermógenes David de Oliveira: conceptualization, formal analysis, data curation, supervision, funding acquisition, writing—initial draft and writing—review and editing.

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Correspondence to Hermógenes David de Oliveira.

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de Souza, A.Á., Lima, A.M., dede Oliveira BezerraSousa, D. et al. Chia (Salvia hispanica L.) Seeds Contain a Highly Stable Trypsin Inhibitor with Potential for Bacterial Management Alone or in Drug Combination Therapy with Oxacillin. Probiotics & Antimicro. Prot. 15, 1221–1233 (2023). https://doi.org/10.1007/s12602-022-09979-5

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