Reiter Jana, Borlinghaus Jan, Dörner Philipp, Schröder Wolfgang, Gruhlke Martin C H, Klaas Michael, Slusarenko Alan J
Department of Plant Physiology (Bio3), RWTH Aachen University, D-52074 Aachen, Germany.
Institute of Aerodynamics, RWTH Aachen University, D-52074 Aachen, Germany.
Exp Ther Med. 2020 Feb;19(2):1541-1549. doi: 10.3892/etm.2019.8387. Epub 2019 Dec 27.
Allicin is a natural antibiotic produced by garlic as a defence against pathogens and pests. Due to the worldwide increase in antibiotic resistance, new antibiotics are desperately required. Allicin is such a candidate and is active against several multidrug-resistant (MDR) strains of human pathogens, including methicillin-resistant (MRSA). When administered orally, allicin is titrated out by glutathione in the cells and blood, and effective therapeutic concentrations are difficult to achieve at the site of an infection. However, in the case of lung infections, allicin can be delivered directly to pathogens via the pulmonary route. In this study, we designed and constructed an lung test rig, which allowed us to model accurately the exposure of lung air-passage surfaces to allicin and gentamicin, in order to examine the feasibility of combating lung infections by direct inhalation. A prototype test rig of lung bronchi with three bifurcations was constructed, which could be coated internally with a thin layer of bacteria-seeded agar medium. The deposition of antimicrobial aerosols on the modelled bronchial surfaces was followed in preliminary tests without the need for animal experiments. The differential sensitivity of the test bacteria to different antibiotics and the dose-dependency of inhibition was shown using the model. Furthermore, a synergistic effect of allicin vapour and ethanol in inhibiting bacterial growth was demonstrated. The modelling of the axial velocity air-flow distribution correlated with the regions indicating the inhibition of bacterial growth, demonstrating that the model has predictive value and can reduce the requirement for animal sacrifice in pre-clinical trials of novel antibiotics.
大蒜素是大蒜产生的一种天然抗生素，用于抵御病原体和害虫。由于全球抗生素耐药性的增加，迫切需要新的抗生素。大蒜素就是这样一种候选药物，它对几种耐多药（MDR）的人类病原体菌株有效，包括耐甲氧西林金黄色葡萄球菌（MRSA）。口服时，大蒜素会被细胞和血液中的谷胱甘肽中和，难以在感染部位达到有效的治疗浓度。然而，在肺部感染的情况下，大蒜素可以通过肺部途径直接输送到病原体。在本研究中，我们设计并构建了一个肺部试验装置，使我们能够准确模拟肺部气道表面暴露于大蒜素和庆大霉素的情况，以研究通过直接吸入对抗肺部感染的可行性。构建了一个具有三个分支的肺支气管原型试验装置，其内部可以涂覆一层薄薄的接种细菌的琼脂培养基。在初步试验中跟踪了抗菌气雾剂在模拟支气管表面的沉积情况，无需进行动物实验。使用该模型显示了试验细菌对不同抗生素的敏感性差异以及抑制作用的剂量依赖性。此外，还证明了大蒜素蒸气和乙醇在抑制细菌生长方面的协同作用。轴向速度气流分布的建模与表明细菌生长受到抑制的区域相关，表明该模型具有预测价值，可以减少新型抗生素临床前试验中动物牺牲的需求。
