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Inhibition of the MepA efflux pump by limonene demonstrated by in vitro and in silico methods

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Abstract

Bacterial resistance is a natural process carried out by bacteria, which has been considered a public health problem in recent decades. This process can be triggered through the efflux mechanism, which has been extensively studied, mainly related to the use of natural products to inhibit this mechanism. To carry out the present study, the minimum inhibitory concentration (MIC) tests of the compound limonene were performed, through the microdilution methodology in sterile 96-well plates. Tests were also carried out with the association of the compound with ethidium bromide and ciprofloxacin, in addition to the ethidium bromide fluorimetry, and later the molecular docking. From the tests performed, it was possible to observe that the compound limonene presented significant results when associated with ethidium bromide and the antibiotic used. Through the fluorescence emission, it was observed that when associated with the compound limonene, a greater ethidium bromide fluorescence was emitted. Finally, when analyzing the in silico study, it demonstrated that limonene can efficiently fit into the MepA structure. In this way, it is possible to show that limonene can contribute to cases of bacterial resistance through an efflux pump, so that it is necessary to carry out more studies to prove its effects against bacteria carrying an efflux pump and assess the toxicity of the compound.

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Authors and Affiliations

  1. Department of Biological Chemistry, Regional University of Cariri - URCA, Rua Cel. Antonio Luis 1161, PimentaCrato-CE, 63105-000, Brazil

    Priscilla Ramos Freitas, Ana Carolina Justino de Araújo, Cristina Rodrigues dos Santos Barbosa, Débora Feitosa Muniz, Ray Silva de Almeida, Irwin Rose Alencar de Menezes, José Galberto Martins da Costa, Fabiola Fernandes Galvão Rodrigues, Janaína Esmeraldo Rocha, Saulo Relison Tintino & Henrique Douglas Melo Coutinho

  2. Centro de Ciências Agrárias E da Biodiversidade, Federal University of Cariri – UFCA, Crato-CE, Brazil

    Francisco Nascimento Pereira-Junior

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  1. Priscilla Ramos Freitas
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  2. Ana Carolina Justino de Araújo
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  3. Cristina Rodrigues dos Santos Barbosa
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  4. Débora Feitosa Muniz
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  5. Ray Silva de Almeida
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  7. José Galberto Martins da Costa
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  8. Fabiola Fernandes Galvão Rodrigues
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  10. Francisco Nascimento Pereira-Junior
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  11. Saulo Relison Tintino
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  12. Henrique Douglas Melo Coutinho
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Correspondence to Henrique Douglas Melo Coutinho.

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Freitas, P.R., de Araújo, A.C.J., dos Santos Barbosa, C.R. et al. Inhibition of the MepA efflux pump by limonene demonstrated by in vitro and in silico methods. Folia Microbiol 67, 15–20 (2022). https://doi.org/10.1007/s12223-021-00909-6

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  • DOI: https://doi.org/10.1007/s12223-021-00909-6

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