Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
Department of Genetics, Harvard Medical School, Boston, MA 02114.
Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3784-3792. doi: 10.1073/pnas.1815656116. Epub 2019 Feb 11.
In their natural habitat of rotting fruit, the nematode feeds on the complex bacterial communities that thrive in this rich growth medium. Hundreds of diverse bacterial strains cultured from such rotting fruit allow growth and reproduction when tested individually. In screens for responses to single bacterial strains associated with nematodes in fruit, we found that causes a genome instability phenotype; we observed abnormally long or fragmented intestinal nuclei due to aberrant nuclear division, or defective karyokinesis. The karyokinesis defects were restricted to intestinal cells and required close proximity between bacteria and the worm. A genetic screen for mutations that cause the same intestinal karyokinesis defect followed by genome sequencing of the isolated mutant strains identified mutations that disrupt DNA damage repair pathways, suggesting that may cause DNA damage in intestinal cells. We hypothesized that such DNA damage is caused by reactive oxygen species produced by and found that hydrogen peroxide added to benign can cause the same intestinal karyokinesis defects in WT Supporting this model, free radical scavengers suppressed the -induced DNA damage. Thus, may signal to eukaryotic hosts via reactive oxygen species, and the host may respond with DNA damage repair pathways.
在腐烂水果的自然栖息地中,这种线虫以在这种丰富的生长介质中茁壮成长的复杂细菌群落为食。从这种腐烂水果中培养的数百种不同的细菌菌株在单独测试时允许生长和繁殖。在针对与水果中线虫相关的单一细菌菌株的 反应筛选中,我们发现 导致基因组不稳定性表型; 我们观察到由于异常核分裂或有缺陷的核胞质分裂导致的异常长或碎片化的肠核。核胞质分裂缺陷仅限于肠细胞,并且需要细菌和蠕虫之间的紧密接近。导致相同肠道核胞质分裂缺陷的 突变的遗传筛选,随后对分离的突变株进行基因组测序,鉴定出破坏 DNA 损伤修复途径的突变,表明 可能导致肠道细胞中的 DNA 损伤。我们假设这种 DNA 损伤是由 产生的活性氧引起的,并发现添加到良性 的过氧化氢可以在 WT 中引起相同的肠道核胞质分裂缺陷,支持这一模型,自由基清除剂抑制了 -诱导的 DNA 损伤。因此, 可能通过活性氧向真核宿主发出信号,宿主可能通过 DNA 损伤修复途径做出反应。