UMR1043, Inserm USC 1360, INRA UMR 5282, CNRS UPS, Centre de Physiopathologie de Toulouse Purpan, UPS, Université de Toulouse EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
UMR1043, Inserm USC 1360, INRA UMR 5282, CNRS UPS, Centre de Physiopathologie de Toulouse Purpan, UPS, Université de Toulouse.
J Infect Dis. 2014 Jul 15;210(2):285-94. doi: 10.1093/infdis/jiu071. Epub 2014 Jan 31.
Sepsis is a life-threatening infection. Escherichia coli is the first known cause of bacteremia leading to sepsis. Lymphopenia was shown to predict bacteremia better than conventional markers of infection. The pks genomic island, which is harbored by extraintestinal pathogenic E. coli (ExPEC) and encodes the genotoxin colibactin, is epidemiologically associated with bacteremia. To investigate a possible relationship between colibactin and lymphopenia, we examined the effects of transient infection of lymphocytes with bacteria that were and those that were not producing the genotoxin. A mouse model of sepsis was used to compare the virulence of a clinical ExPEC isolate with its isogenic mutant impaired for the production of colibactin. We observed that colibactin induced double-strand breaks in the DNA of infected lymphocytes, leading to cell cycle arrest and to cell death by apoptosis. E. coli producing colibactin induced a more profound lymphopenia in septicemic mice, compared with the isogenic mutant unable to produce colibactin. In a sepsis model in which the mice were treated by rehydration and antibiotics, the production of colibactin by the bacteria was associated with a significantly lower survival rate. In conclusion, we demonstrate that production of colibactin by E. coli exacerbates lymphopenia associated with septicemia and could impair the chances to survive sepsis.
败血症是一种危及生命的感染。大肠杆菌是已知的导致败血症的菌血症的第一个原因。淋巴细胞减少症比感染的常规标志物更能预测菌血症。pks 基因组岛存在于肠外致病性大肠杆菌（ExPEC）中，并编码遗传毒素 colibactin，与菌血症在流行病学上有关。为了研究 colibactin 与淋巴细胞减少症之间可能存在的关系，我们研究了短暂感染产生和不产生遗传毒素的细菌对淋巴细胞的影响。我们使用败血症的小鼠模型比较了临床 ExPEC 分离株与其不能产生 colibactin 的同源突变体的毒力。我们观察到 colibactin 诱导感染淋巴细胞的 DNA 双链断裂，导致细胞周期停滞和细胞凋亡。与不能产生 colibactin 的同源突变体相比，产生 colibactin 的大肠杆菌在败血症小鼠中引起更严重的淋巴细胞减少症。在对小鼠进行补液和抗生素治疗的败血症模型中，细菌产生的 colibactin 与生存率显著降低相关。总之，我们证明了大肠杆菌产生的 colibactin 可加重与败血症相关的淋巴细胞减少症，并可能降低对败血症的生存机会。
