Gill Simren K, Hui Kailyn, Farne Hugo, Garnett James P, Baines Deborah L, Moore Luke S P, Holmes Alison H, Filloux Alain, Tregoning John S
Mucosal Infection &Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
Sci Rep. 2016 Jun 8;6:27636. doi: 10.1038/srep27636.
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.
糖尿病与因细菌性肺部感染而住院的频率增加有关。我们推测，高血糖导致气道葡萄糖增加会致使细菌载量上升。在重症监护患者中，我们观察到血糖高时呼吸道细菌定植的可能性显著更高。我们构建了铜绿假单胞菌PAO1株中影响葡萄糖摄取和代谢的基因（oprB、gltK、gtrS和glk）的突变体。这些突变体在以葡萄糖作为唯一碳源的基本培养基中生长减弱。使用链脲佐菌素诱导的高血糖小鼠来测试葡萄糖对体内生长的影响，这些小鼠的气道葡萄糖显著更高。当感染野生型而非突变型PAO1时，高血糖动物的细菌负荷高于对照动物。对高血糖动物进行二甲双胍预处理可降低气道葡萄糖和细菌载量。这些数据支持气道葡萄糖是糖尿病期间细菌载量增加的关键决定因素。
