Modulatory Effect of Croton heliotropiifolius Kunth Ethanolic Extract on Norfloxacin Resistance in Staphylococcus aureus

Samara Barbosa de Brito; Felipe Araújo de Oliveira Alcântara; Antonio Linkoln Alves Borges Leal; Kaliny Henri da Silva Veloso; Leonardo da Rocha Sousa; Ana Paula de Oliveira; Alan Diego da Conceição Santos; Lívia Macedo Dutra; Jackson Roberto Guedes da Silva Almeida; Carlos Emídio Sampaio Nogueira; João Sammy Nery de Souza; Natália Cruz-Martins; Daniel Dias Rufino Arcanjo; Humberto Medeiros Barreto

doi:10.3390/ddc3010001

Drugs and Drug Candidates (Dec 2023)

Modulatory Effect of Croton heliotropiifolius Kunth Ethanolic Extract on Norfloxacin Resistance in Staphylococcus aureus

Samara Barbosa de Brito,
Felipe Araújo de Oliveira Alcântara,
Antonio Linkoln Alves Borges Leal,
Kaliny Henri da Silva Veloso,
Leonardo da Rocha Sousa,
Ana Paula de Oliveira,
Alan Diego da Conceição Santos,
Lívia Macedo Dutra,
Jackson Roberto Guedes da Silva Almeida,
Carlos Emídio Sampaio Nogueira,
João Sammy Nery de Souza,
Natália Cruz-Martins,
Daniel Dias Rufino Arcanjo,
Humberto Medeiros Barreto

Affiliations

Samara Barbosa de Brito: Laboratory of Research in Microbiology, Department of Parasitology and Microbiology, Health Sciences Center, Federal University of Piauí, Teresina 64049-550, PI, Brazil
Felipe Araújo de Oliveira Alcântara: Laboratory of Research in Microbiology, Department of Parasitology and Microbiology, Health Sciences Center, Federal University of Piauí, Teresina 64049-550, PI, Brazil
Antonio Linkoln Alves Borges Leal: Laboratory of Research in Microbiology, Department of Parasitology and Microbiology, Health Sciences Center, Federal University of Piauí, Teresina 64049-550, PI, Brazil
Kaliny Henri da Silva Veloso: Postgraduate Program in Pharmaceutical Sciences, Health Sciences Center, Federal University of Piauí, Teresina 64049-550, PI, Brazil
Leonardo da Rocha Sousa: LAFMOL–Laboratory of Functional and Molecular Studies in Physiopharmacology, Department of Biophysics and Physiology, Federal University of Piaui, Teresina 64049-550, PI, Brazil
Ana Paula de Oliveira: Center for Studies and Research of Medicinal Plants (NEPLAME), Federal University of Vale do São Francisco, Petrolina 56304-205, PE, Brazil
Alan Diego da Conceição Santos: Center for Studies and Research of Medicinal Plants (NEPLAME), Federal University of Vale do São Francisco, Petrolina 56304-205, PE, Brazil
Lívia Macedo Dutra: Center for Studies and Research of Medicinal Plants (NEPLAME), Federal University of Vale do São Francisco, Petrolina 56304-205, PE, Brazil
Jackson Roberto Guedes da Silva Almeida: Center for Studies and Research of Medicinal Plants (NEPLAME), Federal University of Vale do São Francisco, Petrolina 56304-205, PE, Brazil
Carlos Emídio Sampaio Nogueira: Department of Biological Chemistry, Regional University of Cariri, Crato 63100-00, CE, Brazil
João Sammy Nery de Souza: Laboratory of Chemistry, Department of Chemistry, Center for Natural Sciences, Federal University of Piauí, Teresina 64049-550, PI, Brazil
Natália Cruz-Martins: Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Daniel Dias Rufino Arcanjo: Postgraduate Program in Pharmaceutical Sciences, Health Sciences Center, Federal University of Piauí, Teresina 64049-550, PI, Brazil
Humberto Medeiros Barreto: Laboratory of Research in Microbiology, Department of Parasitology and Microbiology, Health Sciences Center, Federal University of Piauí, Teresina 64049-550, PI, Brazil

DOI: https://doi.org/10.3390/ddc3010001
Journal volume & issue: Vol. 3, no. 1
pp. 1 – 12

Abstract

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The high frequency of infectious diseases has spurred research into effective tactics to combat microorganisms that are resistant to several drugs. The overproduction of the transmembrane efflux pump protein NorA, which may export hydrophilic fluoroquinolones, is a common mechanism of resistance in S. aureus strains. This work evaluated the antimicrobial activity of the ethanolic extract from the leaves of Croton heliotropiifolius (EECH) against different bacterial and fungal strains, as well as investigating its modulating effect on the resistance to norfloxacin in a Staphylococcus aureus SA1199B overproducing the NorA efflux pump. Microdilution assays were used to assess the EECH’s antibacterial efficacy. The MIC of norfloxacin or ethidium bromide (EtBr) against the SA1199B strain was determined in the presence or absence of the EECH in order to assess the modifying influence on drug resistance. The EECH showed no activity against the Gram-positive and Gram-negative bacterial strains tested. The EECH also showed no antifungal activity against Candida albicans ATCC 10231. On the other hand, the extract reduced the MIC values for norfloxacin against SA1199B at subinhibitory concentrations. In addition, the EECH also reduced the MIC values of EtBr at subinhibitory concentrations, suggesting the occurrence of phytochemicals that inhibit efflux pumps. Molecular docking showed that retusin, a flavonoid found in the extract, could compete with norfloxacin at the orthosteric site of the NorA, indicating that it could be a potential efflux pump inhibitor. However, isolated retusin did not enhance the activity of norfloxacin or EtBr and it did not inhibit the EtBr efflux, showing that it is not a NorA inhibitor. Even though C. heliotropiifolius is a source of phytochemicals that function as adjuvants for norfloxacin, isolated retusin cannot be used in conjunction with norfloxacin to treat infections brought on by S. aureus that overproduces NorA.

Published in Drugs and Drug Candidates

ISSN: 2813-2998 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pharmacy and materia medica; Science: Chemistry
Website: https://www.mdpi.com/journal/ddc

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