Instituto Gulbenkian de Ciência, R. Q.ta Grande 6, 2780-156, Oeiras, Portugal.
CEDOC, NOVA Medical School Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal.
Sci Rep. 2017 Jul 3;7(1):4504. doi: 10.1038/s41598-017-04081-1.
Escherichia coli is both a harmless commensal in the intestines of many mammals, as well as a dangerous pathogen. The evolutionary paths taken by strains of this species in the commensal-to-pathogen transition are complex and can involve changes both in the core genome, as well in the pan-genome. One way to understand the likely paths that a commensal strain of E. coli takes when evolving pathogenicity is through experimentally evolving the strain under the selective pressures that it will have to withstand as a pathogen. Here, we report that a commensal strain, under continuous pressure from macrophages, recurrently acquired a transposable element insertion, which resulted in two key phenotypic changes: increased intracellular survival, through the delay of phagosome maturation and increased ability to escape macrophages. We further show that the acquisition of the pathoadaptive traits was accompanied by small but significant changes in the transcriptome of macrophages upon infection. These results show that under constant pressures from a key component of the host immune system, namely macrophage phagocytosis, commensal E. coli rapidly acquires pathoadaptive mutations that cause transcriptome changes associated to the host-microbe duet.
大肠杆菌既是许多哺乳动物肠道中无害的共生菌，也是一种危险的病原体。该物种在从共生菌到病原体的转变过程中所采取的进化途径是复杂的，可能涉及核心基因组和泛基因组的变化。了解当共生大肠杆菌菌株进化为致病性时可能采取的途径的一种方法是在该菌株作为病原体必须承受的选择性压力下通过实验使其进化。在这里，我们报告说，在巨噬细胞的持续压力下，一种共生菌株反复获得了转座元件插入，这导致了两个关键的表型变化：通过延迟吞噬体成熟和增加逃离巨噬细胞的能力，从而提高了细胞内存活率。我们进一步表明，获得病原适应性特征伴随着感染时巨噬细胞转录组的微小但显著的变化。这些结果表明，在宿主免疫系统的关键组成部分——巨噬细胞吞噬作用的持续压力下，共生大肠杆菌迅速获得导致与宿主-微生物二重奏相关的转录组变化的病原适应性突变。
