School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, 99164-7520, WA, USA.
Sci Rep. 2017 Oct 31;7(1):14777. doi: 10.1038/s41598-017-14646-9.
Accurate repair of DNA damage is crucial to ensure genome stability and cell survival of all organisms. Bile functions as a defensive barrier against intestinal colonization by pathogenic microbes. Campylobacter jejuni, a leading bacterial cause of foodborne illness, possess strategies to mitigate the toxic components of bile. We recently found that growth of C. jejuni in medium with deoxycholate, a component of bile, caused DNA damage consistent with the exposure to reactive oxygen species. We hypothesized that C. jejuni must repair DNA damage caused by reactive oxygen species to restore chromosomal integrity. Our efforts focused on determining the importance of the putative AddAB DNA repair proteins. A C. jejuni addAB mutant demonstrated enhanced sensitivity to deoxycholate and was impaired in DNA double strand break repair. Complementation of the addAB mutant restored resistance to deoxycholate, as well as function of the DNA double strand break repair system. The importance of these findings translated to the natural host, where the AddAB system was found to be required for efficient C. jejuni colonization of the chicken intestine. This research provides new insight into the molecular mechanism utilized by C. jejuni, and possibly other intestinal pathogens, to survive in the presence of bile.
准确修复 DNA 损伤对于确保所有生物体的基因组稳定性和细胞存活至关重要。胆汁在防止肠道定植致病性微生物方面发挥着防御屏障的作用。空肠弯曲菌是导致食源性疾病的主要细菌病原体之一,它拥有减轻胆汁毒性成分的策略。我们最近发现,空肠弯曲菌在含有脱氧胆酸盐(胆汁的一种成分)的培养基中生长会导致与活性氧暴露一致的 DNA 损伤。我们假设空肠弯曲菌必须修复活性氧引起的 DNA 损伤,以恢复染色体的完整性。我们的努力集中在确定假定的 AddAB DNA 修复蛋白的重要性上。空肠弯曲菌 addAB 突变体对脱氧胆酸盐的敏感性增强,并且在 DNA 双链断裂修复中受损。addAB 突变体的互补恢复了对脱氧胆酸盐的抗性,以及 DNA 双链断裂修复系统的功能。这些发现对天然宿主具有重要意义,因为 AddAB 系统对于空肠弯曲菌在鸡肠道中的有效定植是必需的。这项研究为空肠弯曲菌(可能还有其他肠道病原体)在胆汁存在下生存所利用的分子机制提供了新的见解。