GC-MS Profile and Enhancement of Antibiotic Activity by the Essential Oil of <i>Ocotea odorífera</i> and Safrole: Inhibition of <i>Staphylococcus aureus</i> Efflux Pumps
Ray S. Almeida,
Priscilla R. Freitas,
Ana Carolina J. Araújo,
Irwin R. Alencar Menezes,
Eduardo L. Santos,
Saulo R. Tintino,
Talysson F. Moura,
Jaime R. Filho,
Vitória A. Ferreira,
Ana Cristina A. Silva,
Luiz E. Silva,
Wanderlei do Amaral,
Cícero Deschamps,
Marcello Iriti,
Henrique D. Melo Coutinho
Affiliations
Ray S. Almeida
Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, Brazil
Priscilla R. Freitas
Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, Brazil
Ana Carolina J. Araújo
Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, Brazil
Irwin R. Alencar Menezes
Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, Brazil
Eduardo L. Santos
Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, Brazil
Saulo R. Tintino
Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, Brazil
Talysson F. Moura
Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, Brazil
Jaime R. Filho
Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador 40296-710, Brazil
Vitória A. Ferreira
Department of Biomedicine, Christus University Center-Unichristus, Fortaleza 60190-060, Brazil
Ana Cristina A. Silva
Department of Biomedicine, Maurício de Nassau College-UNINASSAU, Petrolina 58401-115, Brazil
Luiz E. Silva
Post Graduate Program in Sustainable Territorial Development, Federal University of Paraná–UFPR, Matinhos 59950-000, Brazil
Wanderlei do Amaral
Post Graduate Program in Sustainable Territorial Development, Federal University of Paraná–UFPR, Matinhos 59950-000, Brazil
Cícero Deschamps
Department of Chemistry, Post Graduate Program in Agronomy, Federal University of Paraná-UFPR, Curitiba 80011970, Brazil
Marcello Iriti
Department of Agricultural and Environmental Sciences, Milan State University, via G. Celoria 2, 20133 Milan, Italy
Henrique D. Melo Coutinho
Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, Brazil
Considering the evidence that essential oils, as well as safrole, could modulate bacterial growth in different resistant strains, this study aims to characterize the phytochemical profile and evaluate the antibacterial and antibiotic-modulating properties of the essential oil Ocotea odorífera (EOOO) and safrole against efflux pump (EP)-carrying strains. The EOOO was extracted by hydrodistillation, and the phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GC-MS). The antibacterial and antibiotic-modulating activities of the EOOO and safrole against resistant strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were analyzed through the broth microdilution method. The EP-inhibiting potential of safrole in association with ethidium bromide or antibiotics was evaluated using the S. aureus 1199B and K2068 strains, which carry genes encoding efflux proteins associated with antibiotic resistance to norfloxacin and ciprofloxacin, respectively. A reduction in the MIC of ethidium bromide or antibiotics was used as a parameter of EP inhibition. The phytochemical analysis identified 16 different compounds in the EOOO including safrole as the principal constituent. While the EOOO and safrole exerted clinically relevant antibacterial effects against S. aureus only, they potentiated the antibacterial activity of norfloxacin against all strains evaluated by our study. The ethidium bromide and antibiotic assays using the strains of S. aureus SA1119B and K2068, as well as molecular docking analysis, indicated that safrole inhibits the NorA and MepA efflux pumps in S. aureus. In conclusion, Ocotea odorifera and safrole presented promising antibacterial and antibiotic-enhancing properties, which should be explored in the development of drugs to combat antibacterial resistance, especially in strains bearing genes encoding efflux proteins.
