Selective activity of nerolidol-rich Baccharis dracunculifolia essential oils against Gram-Positive bacteria and in silico identification of FabF/KAS-II as a predicted molecular target

The global dissemination of multidrug-resistant bacteria drives the search for novel antibacterial scaffolds. Essential oils (EOs) represent a promising source for developing new agents due to their chemical complexity and multi-target effects. Here, EOs were extracted from the aerial parts of Baccharis dracunculifolia DC. via steam distillation from three natural populations in Minas Gerais, Brazil: Santana do Campestre (EO-SAN), Viçosa (EO-VI), and Belisário (EO-BE). Gas chromatography–mass spectrometry (GC–MS) analysis identified 17 volatile constituents representing 87.70–93.17% of the total chromatographic peak area (87.70% for EO-SAN, 93.17% for EO-VI, and 89.94% for EO-BE), revealing a consistent (E)-nerolidol-rich chemotype (23.75–31.88%). The EOs exhibited potent, selective activity against Gram- positive strains, particularly Streptococcus agalactiae (MIC = MBC = 0.06 µL mL-1 for all oils) and S. hyicus (MIC = 0.06 µL mL-1 for EO-BE; MIC = MBC = 0.12 µL mL-1 for EO-SAN and EO-VI). Gram-negative bacteria were unaffected (MIC >125 µL mL-1; >12.5% v/v). Dynamic growth-kinetic monitoring further corroborated concentration-dependent growth-suppression profiles over 24 h. For S. hyicus, 0.06 µL mL-1 represented 1× MIC for EO-BE (maintaining sustained growth suppression), whereas for EO-SAN and EO-VI it represented a subinhibitory concentration (0.5× MIC), consistent with the partial growth recovery observed under continuous agitation. Pharmacophore-based ligand screening against the Protein Data Bank prioritized β-ketoacyl-[acyl carrier protein] synthase II (FabF/KAS-II) as a predicted molecular target. Molecular docking on modeled FabF/KAS-II revealed that nerolidol occupies the acyl-ACP binding tunnel, engaging conserved catalytic histidines with predicted affinities (≈ −6.2 kcal mol−1; estimated Ki ≈ 28.5 µM) comparable to cerulenin (ΔG = −6.1 kcal mol−1; K ≈ 33.7 µM). In silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses indicated high predicted oral absorption, low genotoxicity, and low acute oral toxicity (predicted LD50 = 5000 mg kg−1). These combined in vitro and in silico findings propose a predicted multi-target model involving envelope perturbation and FabF/KAS-II target engagement, supporting nerolidol-rich B. dracunculifolia EOs as promising scaffolds against Gram-positive pathogens.