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Antimicrobial, Antibiofilm Activities and Synergic Effect of Triterpene 3β,6β,16β-trihydroxyilup-20(29)-ene Isolated from Combretum leprosum Leaves Against Staphylococcus Strains

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Abstract

Antimicrobial resistance is a natural phenomenon and is becoming a huge global public health problem, since some microorganisms not respond to the treatment of several classes of antibiotics. The objective of the present study was to evaluate the antibacterial, antibiofilm, and synergistic effect of triterpene 3β,6β,16β-trihydroxyilup-20(29)-ene (CLF1) against Staphylococcus aureus and Staphylococcus epidermidis strains. Bacterial susceptibility to CLF1 was evaluated by minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) assay. In addition, the effect combined with antibiotics (ampicillin and tetracycline) was verified by the checkerboard method. The biofilms susceptibility was assessed by enumeration of colony-forming units (CFUs) and quantification of total biomass by crystal violet staining. The compound showed bacteriostatic and bactericidal activity against all Staphylococcal strains tested. The synergistic effect with ampicillin was observed only for S. epidermidis strains. Moreover, CLF1 significantly inhibited the biofilm formation and disrupted preformed biofilm of the all strains. Scanning electron microscopy (SEM) images showed changes in the cell morphology and structure of S. aureus ATCC 700698 biofilms (a methicillin-resistant S. aureus strain). Molecular docking simulations showed that CLF1 has a more favorable interaction energy than the antibiotic ampicillin on penicillin-binding protein (PBP) 2a of MRSA, coupled in different regions of the protein. Based on the results obtained, CLF1 proved to be a promising antimicrobial compound against Staphylococcus biofilms.

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Acknowledgements

The authors are grateful to Northeastern Center for the Application and Use of Nuclear Magnetic Resonance (CENAUREMN) for NMR data. Edson Holanda Teixeira is a Senior researcher of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The authors thank Editage (www.editage.com) for English language editing and Central AnalaliticaUFC/CT-INFRA/MCTI-SISNANO/Pro-Equipamentos CAPES.

Funding

This research was funded by Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP) from the PQ/BPI-FUNCAP (Grant#: BP4-0172-00075.01.00/20 for Hélcio Silva dos Santos), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (Grant#: 429670/2018-4), and FAPEMIG (Grant#: APQ-00224-2 for Mayron Alves de Vasconcelos).

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Authors and Affiliations

  1. Laboratório Integrado de Biomoléculas, Departamento de Patologia e Medicina Legal, Universidade Federal do Ceará, Fortaleza, CE, Brazil

    Edson Holanda Teixeira, Alexandre Lopes Andrade, Rafael Pereira, Livia Pontes Farias, Gabrieli Sobral Monteiro & Mayron Alves de Vasconcelos

  2. Universidade do Estado de Minas Gerais, Unidade de Divinopolis, Divinopolis, MG, 35501-179, Brazil

    Mayron Alves de Vasconcelos

  3. Faculdade de Ciências Exatas e Naturais, Universidade do Estado do Rio Grande do Norte, Mossoró, RN, 59610-210, Brazil

    Mayron Alves de Vasconcelos

  4. Faculdade de Educação, Ciência e Letras de Iguatu, Universidade Estadual do Ceará, Iguatu, Ceará, Brazil

    Marcia Machado Marinho

  5. Faculdade de Filosofia Dom Aureliano Matos, Universidade Estadual do Ceará, Limoeiro do Norte, Ceará, Brazil

    Emmanuel Silva Marinho

  6. Centro de Ciências Exatas e Tecnologia, Universidade Estadual Vale do Acaraú, Sobral, Ceará, Brazil

    Hélcio Silva Santos

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  1. Edson Holanda Teixeira
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Contributions

RP, ALA, and HSS contributed in the isolation and characterization of the compound. RP, ALA, LPF, and GSM contributed in antibacterial and antibiofilm activities and writing of the manuscript. MMM and ESM contributed in computational assay and writing of the manuscript. EHT, HSS, and MAV contributed in the analysis of the data, critical reading and draft of the manuscript, and design the study and supervised the laboratory work.

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Teixeira, E.H., Andrade, A.L., Pereira, R. et al. Antimicrobial, Antibiofilm Activities and Synergic Effect of Triterpene 3β,6β,16β-trihydroxyilup-20(29)-ene Isolated from Combretum leprosum Leaves Against Staphylococcus Strains. Curr Microbiol 80, 176 (2023). https://doi.org/10.1007/s00284-023-03284-2

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