Department of Biotechnology, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Paterna, Valencia, Spain.
Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Barcelona, Spain.
Sci Rep. 2024 Jul 23;14(1):16945. doi: 10.1038/s41598-024-67731-1.
Several pathogenic Escherichia coli strains cause diarrhea. Enteroaggregative E. coli (EAEC) strains are one of the diarrheagenic pathotypes. EAEC cells form a "stacked-brick" arrangement over the intestinal epithelial cells. EAEC isolates express, among other virulence determinants, the AggR transcriptional activator and the aggregative adherence fimbriae (AAF). Overexpression of the aggR gene results in increased expression of virulence factors such as the aff genes, as well as several genes involved in specific metabolic pathways such as fatty acid degradation (fad) and arginine degradation (ast). To support the hypothesis that induction of the expression of some of these pathways may play a role in EAEC virulence, in this study we used a murine infection model to evaluate the impact of the expression of these pathways on infection parameters. Mice infected with a mutant derivative of the EAEC strain 042, characterized by overexpression of the aggR gene, showed increased disease symptoms compared to those exhibited by mice infected with the wild type (wt) strain 042. Several of these symptoms were not increased when the infecting mutant, which overexpressed aggR, lacked the fad and ast pathways. Therefore, our results support the hypothesis that different metabolic pathways contribute to EAEC virulence.
几种致病性大肠杆菌菌株可引起腹泻。肠聚集性大肠杆菌(EAEC)菌株是一种致腹泻型病原体。EAEC 细胞在肠上皮细胞上形成“堆积砖”排列。EAEC 分离株表达包括 AggR 转录激活因子和聚集性粘附菌毛(AAF)在内的多种毒力决定因素。aggR 基因的过度表达导致毒力因子如 aff 基因以及参与特定代谢途径(如脂肪酸降解( fad )和精氨酸降解( ast ))的几个基因的表达增加。为了支持诱导这些途径中的一些表达可能在 EAEC 毒力中起作用的假设,在这项研究中,我们使用了一种小鼠感染模型来评估这些途径的表达对感染参数的影响。与感染野生型(wt)菌株 042 的小鼠相比,感染过表达 aggR 基因的 EAEC 菌株 042 突变体衍生物的小鼠表现出更严重的疾病症状。当感染缺乏 fad 和 ast 途径的过表达 aggR 的突变体时,其中一些症状并未增加。因此,我们的结果支持这样一种假设,即不同的代谢途径有助于 EAEC 的毒力。