Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections
Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections
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DOI：
10.1099/mic.0.27955-0
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发表时间：
2005-12-01
期刊：
影响因子：
2.8
通讯作者：
Givskov, M
中科院分区：
文献类型：
--
作者：
Bjarnsholt, T;Jensen, PO;Givskov, M
人类机会致病菌铜绿假单胞菌是囊性纤维化患者慢性肺部感染的主要微生物。铜绿假单胞菌通过在整个肺中形成生物膜小菌落来定殖肺。群体感应（QS）使生物膜细菌对其他致死剂量的抗生素具有高度耐受性，并保护免受多形核白细胞（PMN）的杀菌活性。先前已经证明，大蒜提取物抑制QS。在这项研究中，大蒜和妥布霉素的协同作用，和中性粒细胞的活动进行了评估。铜绿假单胞菌生长在体外连续培养直流流动室与大蒜提取物和不。大蒜处理的生物膜对妥布霉素和PMN放牧都敏感。此外，当与大蒜处理的生物膜一起孵育时，PMNs显示呼吸爆发激活增加。施用大蒜提取物作为小鼠肺部感染模型的治疗。用大蒜提取物或安慰剂处理小鼠7天，在将铜绿假单胞菌滴入小鼠的左肺之前，最初的2天是预防性的。细菌学、死亡率、组织病理学和细胞因子产生被用作指标。大蒜治疗最初引起了更高程度的炎症，并显着改善了感染细菌的清除。结果表明，大蒜的QS抑制提取物使铜绿假单胞菌对妥布霉素敏感，呼吸爆发和PMN的吞噬作用，以及导致肺部感染的改善结果。
The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly tolerant to otherwise lethal doses of antibiotics, and protects against the bactericidal activity of polymorphonuclear leukocytes (PMNs). It has been previously demonstrated that QS is inhibited by garlic extract. In this study, the synergistic effects of garlic and tobramycin, and PMNs activities have been evaluated. P. aeruginosa was grown in vitro in continuous-culture once-through flow chambers with and without garlic extract. The garlic-treated biofilms were susceptible to both tobramycin and PMN grazing. Furthermore, the PMNs showed an increase in respiratory burst activation, when incubated with the garlic-treated biofilm. Garlic extract was administered as treatment for a mouse pulmonary infection model. Mice were treated with garlic extract or placebo for 7 days, with the initial 2 days being prophylactic before P. aeruginosa was instilled in the left lung of the mice. Bacteriology, mortality, histopathology and cytokine production were used as indicators. The garlic treatment initially provoked a higher degree of inflammation, and significantly improved clearing of the infecting bacteria. The results indicate that a QS-inhibitory extract of garlic renders P. aeruginosa sensitive to tobramycin, respiratory burst and phagocytosis by PMNs, as well as leading to an improved outcome of pulmonary infections.