肠道细菌需要适应肠道内胆汁盐的抗菌活性。磷脂酶A(PldA)是维持细菌膜稳态的关键酶。细菌通过调节其膜组成来响应胁迫。空肠弯曲杆菌是全球人类最常见的病因。然而,空肠弯曲杆菌在肠道环境中适应和生存的机制尚不完全清楚。在这项研究中,我们调查了PldA的角色,胆盐脱氧胆酸钠(DOC),和空肠杆菌生物学中的氧气利用率,模仿体内情况。使用生长曲线来确定空肠弯曲杆菌对胆汁盐的适应性。使用RNA-seq和功能测定来研究影响细菌生理的PldA依赖性和DOC诱导的基因表达变化。进行生存研究以解决空肠弯曲杆菌中的氧化应激防御。这里,我们发现在胆汁盐DOC存在下,空肠弯曲杆菌的PldA是最佳生长所必需的。在高氧气条件下,DOC对空肠杆菌有毒,但在低氧条件下,就像存在于肠腔中一样,空肠杆菌受益于DOC。空肠弯曲杆菌PldA似乎能够在DOC存在下使用最佳生长所需的铁,但使细菌更容易受到氧化应激的影响。总之,DOC在低氧条件下刺激空肠弯曲菌生长并以PldA依赖性方式改变菌落形态。空肠杆菌通过以PldA依赖性方式上调铁代谢而受益于DOC。
Enteric bacteria need to adapt to endure the antibacterial activities of bile salts in the gut. Phospholipase A (
PldA) is a key enzyme in the maintenance of bacterial membrane homeostasis. Bacteria respond to stress by modulating their membrane composition. Campylobacter jejuni is the most common cause of human worldwide. However, the mechanism by which C. jejuni adapts and survives in the gut environment is not fully understood. In this study, we investigated the roles of PldA, bile salt sodium deoxycholate (DOC), and oxygen availability in C. jejuni biology, mimicking an in vivo situation. Growth curves were used to determine the adaptation of C. jejuni to bile salts. RNA-seq and functional assays were employed to investigate the
PldA-dependent and DOC-induced changes in gene expression that influence bacterial physiology. Survival studies were performed to address oxidative stress defense in C. jejuni. Here, we discovered that
PldA of C. jejuni is required for optimal growth in the presence of bile salt DOC. Under high oxygen conditions, DOC is toxic to C. jejuni, but under low oxygen conditions, as is present in the lumen of the gut, C. jejuni benefits from DOC. C. jejuni
PldA seems to enable the use of iron needed for optimal growth in the presence of DOC but makes the bacterium more vulnerable to oxidative stress. In conclusion, DOC stimulates C. jejuni growth under low oxygen conditions and alters colony morphology in a PldA-dependent manner. C. jejuni benefits from DOC by upregulating iron metabolism in a
PldA-dependent manner.