Antibacterial Activity of the Essential Oil of <i>Piper tuberculatum</i> Jacq. Fruits against Multidrug-Resistant Strains: Inhibition of Efflux Pumps and β-Lactamase
Lucas Yure Santos da Silva,
Cicera Laura Roque Paulo,
Talysson Felismino Moura,
Daniel Sampaio Alves,
Renata Torres Pessoa,
Isaac Moura Araújo,
Cícera Datiane de Morais Oliveira-Tintino,
Saulo Relison Tintino,
Carla de Fatima Alves Nonato,
José Galberto Martins da Costa,
Jaime Ribeiro-Filho,
Henrique Douglas Melo Coutinho,
Grażyna Kowalska,
Przemysław Mitura,
Marek Bar,
Radosław Kowalski,
Irwin Rose Alencar de Menezes
Affiliations
Lucas Yure Santos da Silva
Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Cicera Laura Roque Paulo
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Talysson Felismino Moura
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Daniel Sampaio Alves
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Renata Torres Pessoa
Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Isaac Moura Araújo
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Cícera Datiane de Morais Oliveira-Tintino
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Saulo Relison Tintino
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Carla de Fatima Alves Nonato
Laboratory Natural Products Research, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
José Galberto Martins da Costa
Laboratory Natural Products Research, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Jaime Ribeiro-Filho
Oswaldo Cruz Foundation (FIOCRUZ), Fiocruz Ceará, R. São José, S/N-Precabura, Eusébio 21040-900, CE, Brazil
Henrique Douglas Melo Coutinho
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Grażyna Kowalska
Department of Tourism and Recreation, University of Life Sciences in Lublin, 15 Akademicka Str., 20-950 Lublin, Poland
Przemysław Mitura
Department of Urology and Oncological Urology, Medical University of Lublin, 8 Jaczewskiego Str., 20-954 Lublin, Poland
Marek Bar
Department of Urology and Oncological Urology, Medical University of Lublin, 8 Jaczewskiego Str., 20-954 Lublin, Poland
Radosław Kowalski
Department of Analysis and Food Quality Assessment, University of Life Sciences in Lublin, 8 Skromna Str., 20-704 Lublin, Poland
Irwin Rose Alencar de Menezes
Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil
Antimicrobial resistance has become a growing public health concern in recent decades, demanding a search for new effective treatments. Therefore, this study aimed to elucidate the phytochemical composition and evaluate the antibacterial activity of the essential oil obtained from the fruits of Piper tuberculatum Jacq. (EOPT) against strains carrying different mechanisms of antibiotic resistance. Phytochemical analysis was performed using gas chromatography–mass spectrometry (GC/MS). The antibacterial activity of EOPT and its ability to inhibit antibiotic resistance was evaluated through the broth microdilution method. The GC-MS analysis identified 99.59% of the constituents, with β-pinene (31.51%), α-pinene (28.38%), and β-cis-ocimene (20.22%) being identified as major constituents. The minimum inhibitory concentration (MIC) of EOPT was determined to assess its antibacterial activity against multidrug-resistant strains of Staphylococcus aureus (IS-58, 1199B, K2068, and K4100). The compound showed a MIC of ≥ 1024 μg/mL, suggesting a lack of intrinsic antibacterial activity. However, when the EOPT was associated with antibiotics and EtBr, a significant decrease in antibiotic resistance was observed, indicating the modulation of efflux pump activity. This evidence was corroborated with the observation of increased fluorescent light emission by the bacterial strains, indicating the involvement of the NorA and MepA efflux pumps. Additionally, the significant potentiation of ampicillin activity against the S. aureus strain K4414 suggests the β-lactamase inhibitory activity of EOPT. These results suggest that the essential oil from P. tuberculatum fruits has antibiotic-enhancing properties, with a mechanism involving the inhibition of efflux pumps and β-lactamase in MDR S. aureus strains. These findings provide new perspectives on the potential use of EOPT against antibiotic resistance and highlight the importance of Piper species as sources of bioactive compounds with promising therapeutic activities against MDR bacteria. Nevertheless, further preclinical (in vivo) studies remain necessary to confirm these in vitro-observed results.
