Increased airway glucose increases airway bacterial load in hyperglycaemia.
Increased airway glucose increases airway bacterial load in hyperglycaemia.
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DOI：
10.1038/srep27636
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发表时间：
2016-06-08
影响因子：
4.6
通讯作者：
Tregoning JS
中科院分区：
文献类型：
--
作者：
Gill SK;Hui K;Farne H;Garnett JP;Baines DL;Moore LS;Holmes AH;Filloux A;Tregoning JS
糖尿病与细菌性肺部感染导致的住院频率增加有关。我们假设高血糖引起的气道葡萄糖增加导致细菌负荷增加。在重症监护患者中，我们观察到当血糖高时呼吸道细菌定植的可能性显著增加。我们在铜绿假单胞菌菌株PAO 1中设计了影响葡萄糖摄取和代谢的基因（oprB、gltK、gtrS和glk）突变体。这些突变体在补充有葡萄糖作为唯一碳源的基本培养基中显示出减弱的生长。使用链脲佐菌素诱导的高血糖小鼠测试了葡萄糖对体内生长的影响，这些小鼠具有显著更高的气道葡萄糖。当感染野生型而非突变型PAO1时，高血糖动物的细菌负荷大于对照动物。高血糖动物的二甲双胍预处理降低了气道葡萄糖和细菌负荷。这些数据支持气道葡萄糖作为糖尿病期间细菌负荷增加的关键决定因素。
Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes.