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A short synthetic peptide, based on LyeTx I from Lycosa erythrognatha venom, shows potential to treat pneumonia caused by carbapenem-resistant Acinetobacter baumannii without detectable resistance

The Journal of Antibiotics volume 74, pages 425–434 (2021)Cite this article

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Abstract

The emergence of antibiotic-resistant bacteria, especially carbapenem-resistant Acinetobacter baumannii (CRAB), together with relative stagnation in the development of effective antibiotics, has led to enormous health and economic problems. In this study, we aimed to describe the antibacterial spectrum of LyeTx I mnΔK, a short synthetic peptide based on LyeTx I from Lycosa erythrognatha venom, against CRAB. LyeTx I mnΔK showed considerable antibacterial activity against extensively resistant A. baumannii, with minimum inhibitory and bactericidal concentrations ranging from 1 to 16 µM and 2 to 32 µM, respectively. This peptide significantly increased the release of 260 nm-absorbing intracellular material from CRAB, suggesting bacteriolysis. LyeTx I mnΔK was shown to act synergistically with meropenem and colistin against CRAB. The cytotoxic concentration of LyeTx I mnΔK against Vero cells (CC50 = 55.31 ± 5.00 µM) and its hemolytic activity (HC50 = 77.07 ± 4.00 µM) were considerably low; however, its antibacterial activity was significantly reduced in the presence of human and animal serum and trypsin. Nevertheless, the inhalation of this peptide was effective in reducing pulmonary bacterial load in a mouse model of CRAB infection. Altogether, these results demonstrate that the peptide LyeTx I mnΔK is a potential prototype for the development of new effective and safe antibacterial agents against CRAB.

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Acknowledgements

We thank also the teacher Jaqueline Maria Siqueira Ferreira (UFSJ-Laboratório de Microbiologia Médica) for carrying out the cytotoxicity test. WGL is grateful to Coordenação de Aperfeiçoamento de Pessoal do Nível Superior (CAPES) for a Ph.D. fellowship, as well as Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), and Pro-Reitoria de Pesquisa of Universidade Federal de Minas Gerais (PRPq/UFMG).

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CNPq, CAPES and FAPEMIG.

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Authors and Affiliations

  1. Laboratório de Radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

    William Gustavo Lima, Valbert Nascimento Cardoso & Simone Odília Antunes Fernandes

  2. Fundação Ezequiel Dias (FUNED), Belo Horizonte, MG, Brazil

    Júlio César Moreira Brito

  3. Faculdade Santa Casa de Belo Horizonte, Programa de Pós-Graduação Stricto Senso de Medicina e Biomedicina, Belo Horizonte, MG, Brazil

    Maria Elena de Lima

  4. Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Belo Horizonte, MG, Brazil

    Amanda Cristina Silva Tardelli Pizarro & Maria Auxiliadora Martins de Mello Vianna

  5. Laboratório de Diagnóstico Laboratorial e Microbiologia Clínica, Universidade Federal de São João del-Rei, Campus Centro-Oeste Dona Lindu, Divinópolis, MG, Brazil

    Magna Cristina de Paiva

  6. Escola de Veterinária, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil

    Débora Cristina Sampaio de Assis

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  1. William Gustavo Lima
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All authors contributed to the development, analysis, and drafting of this paper.

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Correspondence to William Gustavo Lima or Simone Odília Antunes Fernandes.

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The study was approved by the Laboratory Animal Research Ethics Committee of the Federal University of Minas Gerais (CEUA-UFMG: 367/2019).

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Lima, W.G., Brito, J.C.M., de Lima, M.E. et al. A short synthetic peptide, based on LyeTx I from Lycosa erythrognatha venom, shows potential to treat pneumonia caused by carbapenem-resistant Acinetobacter baumannii without detectable resistance. J Antibiot 74, 425–434 (2021). https://doi.org/10.1038/s41429-021-00421-6

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