Tetard Alexandre, Foley Sarah, Mislin Gaëtan L A, Brunel Jean-Michel, Oliva Estefania, Torrealba Anzola Freddy, Zedet Andy, Cardey Bruno, Pellequer Yann, Ramseyer Christophe, Plésiat Patrick, Llanes Catherine
UMR CNRS 6249 Chrono-Environnement, Université Bourgogne Franche-Comté, Besançon, France.
CNRS/Université de Strasbourg UMR 7242 Biotechnologie et Signalisation Cellulaire, Illkirch, France.
Front Microbiol. 2021 Jul 5;12:709838. doi: 10.3389/fmicb.2021.709838. eCollection 2021.
Essential oils (EOs) or their components are widely used by inhalation or nebulization to fight mild respiratory bacterial infections. However, their interaction with antibiotics is poorly known. In this study we evaluated the effects of citral, the main component of lemongrass oil, on susceptibility of to antibiotics. Exposure of strain PA14 to subinhibitory concentrations of citral increased expression of operons encoding the multidrug efflux systems MexEF-OprN and MexXY/OprM, and bacterial resistance to anti-pseudomonal antibiotics including imipenem (twofold), gentamicin (eightfold), tobramycin (eightfold), ciprofloxacin (twofold), and colistin (≥128-fold). Use of pump deletion mutants showed that in addition to efflux other mechanisms were involved in this citral-induced phenotype. Determination of Zeta potential suggested that citral impairs the cell surface binding of aminoglycosides and colistin used at low concentrations (≤10 μg/mL). Moreover, experiments based on Raman spectroscopy and high-resolution mass spectrometry demonstrated formation of a Schiff base between the aldehyde group of citral and amino-groups of tobramycin and colistin. Chemical synthesis of tobracitryl, the imine compound resulting from condensation of citral and tobramycin, confirmed the loss of antibiotic activity due to adduct formation. Altogether these data point to the potential risk concern of self-medication with EOs containing citral in patients suffering from chronic lung infections and being treated with aerosols of aminoglycoside or colistin.
香精油（EOs）或其成分被广泛用于通过吸入或雾化来对抗轻度呼吸道细菌感染。然而，它们与抗生素的相互作用却鲜为人知。在本研究中，我们评估了柠檬草油的主要成分柠檬醛对[细菌名称未给出]对抗生素敏感性的影响。将PA14菌株暴露于亚抑菌浓度的柠檬醛会增加编码多药外排系统MexEF - OprN和MexXY/OprM的操纵子的表达，以及细菌对包括亚胺培南（两倍）、庆大霉素（八倍）、妥布霉素（八倍）、环丙沙星（两倍）和黏菌素（≥128倍）在内的抗假单胞菌抗生素的耐药性。使用泵缺失突变体表明，除了外排作用外，其他机制也参与了这种柠檬醛诱导的表型。Zeta电位的测定表明，柠檬醛会损害低浓度（≤10μg/mL）使用的氨基糖苷类药物和黏菌素与细胞表面的结合。此外，基于拉曼光谱和高分辨率质谱的实验表明，柠檬醛的醛基与妥布霉素和黏菌素的氨基之间形成了席夫碱。柠檬醛与妥布霉素缩合形成的亚胺化合物托布拉西特瑞尔的化学合成证实了由于加合物形成导致抗生素活性丧失。总之，这些数据指出了在患有慢性肺部感染并接受氨基糖苷类药物或黏菌素气雾剂治疗的患者中，自行使用含有柠檬醛的香精油进行自我治疗可能存在的潜在风险问题。
