白念珠菌群体感应分子farnesol研究进展

在自然界,微生物与高等生物一样也具有社会学行为,也能形成一定的群体并发生相互影响、相互作用。群体感应（quorum sensing,QS）是细菌监控自身群体密度的环境信号感受机制。细菌在生长繁殖过程中向细胞外分泌一些特定的化学信号分子（或称信息素）,当信号分子达到一定的阈值时,     

Potentiation of the activity of β-lactam antibiotics by farnesol and its derivatives

Farnesol, a sesquiterpene alcohol, potentiates the activity of β-lactam antibiotics against antibiotic-resistant bacteria. We document that farnesol and two synthetic derivatives (compounds 2 and 6) have poor antibacterial activities of their own, but they potentiate the activities of ampicillin and oxacillin against Staphylococcus aureus strains (including methicillin-resistant S. aureus). These compounds attenuate the rate of growth of bacteria, which has to be taken into account in assessment of the potentiation effect.     

Farnesol production in Escherichia coli through the construction of a farnesol biosynthesis pathway – application of PgpB and YbjG phosphatases

Farnesol is a sesquiterpenoid alcohol that has important industrial and medical potential. It is usually synthesized from farnesyl diphosphate (FPP) by farnesol synthase in plants. FPP accumulation can cause up‐regulation of phosphatases capable of FPP hydrolysis, resulting in farnesol production in Escherichia coli. We found that PgpB and YbjG, two integral membrane phosphatases, can hydrolyze FPP into farnesol. Overexpression of FPP synthase (IspA) and PgpB, along with a heterologous mevalonate pathway, enabled recombinant E. coli to produce 526.1 mg/L of farnesol. This result indicates that the phosphatases PgpB and YbjG can be used to construct a novel farnesol synthesis pathway for mass production in E. coli.     

In vitro and in vivo activity of three sesquiterpenes against L(3) larvae of Anisakis type I

In order to investigate the possible use of terpenic derivatives to treat anisakiasis caused by L₃ larvae of Anisakis, we studied the in vitro and in vivo larvicidal activity of three sesquiterpenes (nerolidol, farnesol and elemol). In vitro experiments included the histological study of larval damage and in vivo studies the measurement of myeloperoxidase activity in rat gastrointestinal tract after administration of the sesquiterpenes. In the in vitro assays, the most active compound against the L₃ larvae was nerolidol, followed by farnesol; both caused the death of all nematodes, which showed cuticle changes and intestinal wall rupture. In the in vivo assays, only 20% of infected rats treated with nerolidol or farnesol showed gastric wall lesions in comparison to 86.6% of control animals. According to these results, nerolidol and farnesol are good candidates for further research as biocidal agents against L₃ larvae of Anisakis type I.     

Farnesol stimulates laccase production in Trametes versicolor

Farnesol, a quorum‐sensing molecule, was used successfully to improve laccase production in submerged cultures of Trametes versicolor. At the optimal farnesol concentration of 60 μM added at the beginning of the culture, the extracellular laccase activity reached 629.3 U L^?1 after 6 days of cultivation, which represented a 1.92‐fold increase relative to the control without farnesol treatment. The addition of farnesol resulted in an increase in the accumulation of H₂O₂ and an increased expression of the laccase (lac) gene and the RhoA gene. The RhoA gene correlated with hyperbranched mycelia, which facilitated the secretion of the intracellular laccase. This study provides a basis for understanding the induction mechanism of farnesol for enhancing laccase production.     

Docking,characterization and investigation of β-cyclodextrin complexed with farnesol,an acyclic sesquiterpene alcohol,produces orofacial antinociceptive profile in experimental protocols

In this study, an inclusion complex with β-cyclodextrin and farnesol (βCD/FAR) was used to improve the physico-chemical and pharmacological properties of farnesol. The samples were obtained using the physical mixture, paste and slurry complexation methods and characterized by variety of methods. To evaluate the pharmacological effect, an animal model of orofacial pain induced by formalin, glutamate and capsaicin was used, and its possible mechanisms of action were evaluated. The slurry complexation method was produced with a formation energy of 3.45 kcal/mol and exhibited a better complexation profile as it presented smaller, deformed crystals compared to the other methods, with a stable complex formed. The formation energy was 3.45 kcal/mol. In the orofacial pain test induced by formalin, capsaicin and glutamate the results show that farnesol and its complex at doses of 50 and 100 mg/kg significantly decreased (p < 0.001) face-rubbing behavior. In the investigation of the mechanism of action, the administration of glibenclamide and ondansetron modified the antinociceptive effect of the farnesol, suggesting the possible participation of the ATP-sensitive K⁺ channel (K⁺_ATP) and 5-hydroxytryptamine (5-HT₃) channels/receptors. A rota-rod test did not show any significant alterations in motor performance in the groups treated with farnesol and its complex. In conclusion, farnesol and βCD/FAR reduced orofacial pain, possibly mediated by K⁺_ATP channels and 5-HT₃ receptors.     

DSCAM: an endogenous promoter drives expression in the developing CNS and neural crest

Farnesol and the related isoprenoids, geranylgeraniol, geranylgeranyl pyrophosphate, and farnesyl pyrophosphate, are produced in the endoplasmic reticulum of hepatocytes in mammals, and each serve important biological functions. Of these compounds, only farnesol was shown to significantly inhibit rabbit liver microsomal cytochrome P450 enzymes. The observed inhibition appeared to be reversible, and was not strictly competitive, but rather mixed in nature. Of the activities examined, ethoxycoumarin de-ethylase and diclofenac-4-hydroxylase activities were most sensitive to farnesol, with K(I) and K(I)' values between 11 and 40 microM. Caffeine-8-hydroxylation and taxol-6-hydroxylation were not inhibited at all by farnesol. Farnesol appeared to be a P450 substrate, as well as an inhibitor, as indicated by the NADPH-dependent decrease in farnesol concentration in microsomal incubations, and the metabolism was inhibited by CO, which pointed to the involvement of P450 isozymes.     

Mosquito larvicidal activities of farnesol and farnesyl acetate via regulation of juvenile hormone receptor complex formation in Aedes mosquito

Due to their target specificity and low-toxicity, insect growth regulators (IGRs) are regarded as promising alternatives to chemical insecticides. In this study, farnesol and farnesyl acetate exhibited juvenile hormone (JH)-based IGR activities. While farnesyl acetate showed JH agonist (JHA) activity in concentration-dependent manner, farnesol was identified as JH antagonist (JHAN) by interfering pyriproxyfen-mediated binding JH receptor complex. Both compounds showed mosquito larvicidal activities and caused retardation of ovarian growth of female Aedes albopictus by modulating the formation of JH receptor complex, expression of JH-inducible genes, and thereby disrupting JH-based endocrine regulations. These results suggested that farnesol and farnesyl acetate could be applicable for investigating underlying mechanisms of JH-regulated insect physiologies as well as developing novel eco-friendly insecticides.