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The objective of this study was to determine the chemical profile and to evaluate the antibacterial activity of the essential oils of Piper species and modulation of the antibiotic activity, using the microdilution method to determine the minimum inhibitory concentration. The chemical components were characterized by gas chromatography coupled to mass spectrometry, which revealed β-copaen-4-α-ol (31.38%), spathulenol (25.92%), and germacrene B (21.53%) as major constituents of the essential oils of Piper arboreum, Piper aduncum, and Piper gaudichaudianum, respectively. The essential oils analyzed in this study did not present a clinically relevant activity against standard and multiresistant Escherichia coli. However, in the case of multiresistant Staphylococcus aureus, there was a significant activity, corroborating with reports in the literature, where Gram-positive bacteria are more susceptible to antimicrobial activity. The essential oils modulated the effect of the antibiotics norfloxacin and gentamicin, having on the latter greater modulating effect; however, for erythromycin, no statistically significant effect was observed. In conclusion, the results obtained in this study demonstrated that the essential oils of the analyzed Piper species present an inhibitory effect against S. aureus and modulate antibiotic activity, most of which presents synergistic activity.

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.

Cdc42, a member of the Rho GTPase family, is an intracellular signaling protein known for its roles in cytoskeleton rearrangements and, more recently, in apoptosis/senescence triggered by genotoxic stress. In some tumor cells, the overactivation of Cdc42 through the expression of constitutively active mutants (G12V or Q61L), GEF activation, or GAP downregulation functions as an antiproliferative or pro-aging mechanism. In this study, human cell lines with different P53 protein profiles were exposed to UV radiation, and the interactions between Cdc42 and proteins that are putatively involved in the DNA damage response and repair mechanisms were screened. The affinity-purified proteins obtained through pull-down experiments of the cell lysates using the recombinant protein baits GST, GST-Cdc42-WT, or GST-Cdc42-G12V were identified by mass spectrometry. The resulting data were filtered and used for the construction of protein–protein interaction networks. Among several promising proteins, three targets, namely, PAK4, PHB-2, and 14-3-3η, which are involved in the cell cycle, apoptosis, DNA repair, and chromatin remodeling processes, were identified. Biochemical validation experiments showed physical and proximal interactions between Cdc42 and the three targets in the cells, particularly after exposure to UV. The results suggest that the molecular mechanisms coordinated by overactivated Cdc42 (with the G12V mutation) to increase the cellular sensitivity to UV radiation and the susceptibility to cell death are collectively mediated by these three proteins. Therefore, the Cdc42 GTPase can potentially be considered another player involved in maintenance of the genomic stability of human cells during exposure to genotoxic stress.