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大蒜可阻断群体感应并促进肺部铜绿假单胞菌感染的快速清除。

Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections.

作者信息

Bjarnsholt Thomas, Jensen Peter Østrup, Rasmussen Thomas B, Christophersen Lars, Calum Henrik, Hentzer Morten, Hougen Hans-Petter, Rygaard Jørgen, Moser Claus, Eberl Leo, Høiby Niels, Givskov Michael

机构信息

Centre for Biomedical Microbiology, BioCentrum, Technical University of Denmark, DK-2800 Lyngby, Denmark.

Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.

出版信息

Microbiology (Reading). 2005 Dec;151(Pt 12):3873-3880. doi: 10.1099/mic.0.27955-0.

Abstract

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.

摘要

机会性人类病原体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部形成生物膜微菌落来定殖。群体感应(QS)使生物膜细菌对原本致死剂量的抗生素具有高度耐受性,并能抵御多形核白细胞(PMN)的杀菌活性。先前已证明大蒜提取物可抑制群体感应。在本研究中,评估了大蒜与妥布霉素的协同作用以及PMN的活性。铜绿假单胞菌在有无大蒜提取物的连续培养单通道流动室中进行体外培养。经大蒜处理的生物膜对妥布霉素和PMN的吞噬均敏感。此外,当与经大蒜处理的生物膜一起孵育时,PMN的呼吸爆发激活增加。大蒜提取物被用作小鼠肺部感染模型的治疗药物。小鼠用大蒜提取物或安慰剂治疗7天,最初2天为预防性治疗,之后将铜绿假单胞菌注入小鼠左肺。将细菌学、死亡率、组织病理学和细胞因子产生用作指标。大蒜治疗最初引发了更高程度的炎症,并显著改善了感染细菌的清除。结果表明,大蒜的群体感应抑制提取物使铜绿假单胞菌对妥布霉素敏感,对PMN的呼吸爆发和吞噬作用敏感,并导致肺部感染的转归得到改善。

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