Key Laboratory of Applied Technology on Green-Eco Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A & F University, Hangzhou, Zhejiang, China.
State Key Laboratory of Subtropical Silviculture, Zhejiang A & F University, Hangzhou, Zhejiang, China.
Appl Environ Microbiol. 2023 Jul 26;89(7):e0056123. doi: 10.1128/aem.00561-23. Epub 2023 Jul 5.
Vibrio cholerae is the causative agent of cholera. Effective intestinal colonization is a key step for V. cholerae pathogenicity and transmission. In this study, we found that deleting , a homolog of the Escherichia coli CsrD protein, caused a V. cholerae colonization defect in the intestine of adult mice. By analyzing the RNA levels of CsrB, CsrC, and CsrD, we found that deleting increased the levels of CsrB and CsrD but decreased the level of CsrC. However, deleting CsrB and -D not only recovered the deletion mutant colonization defect but also recovered CsrC to wild-type levels. These results indicated that controlling the RNA levels of CsrB, -C, and -D is crucial for V. cholerae colonization of adult mice. We further demonstrated that the RNA levels of CsrB and CsrD were mainly controlled by MshH-dependent degradation, yet the level of CsrC was mainly determined by the CsrA-dependent stabilization. Our data show that V. cholerae differentially controls CsrB, -C, and -D abundance through the MshH-CsrB/C/D-CsrA regulatory pathway to finely regulate the activity of CsrA targets such as ToxR, so as to better survive in adult mouse intestine. The ability of V. cholerae to colonize the intestine is a key factor for its fitness and transmissibility between hosts. Here, we investigated the mechanism of V. cholerae colonization of adult mammal intestine and found that precisely controlling the CsrB, -C, and -D contents by MshH and CsrA plays an essential role for V. cholerae colonization in the adult mouse intestine. These data expand our knowledge on the mechanism of V. cholerae controlling the RNA level of CsrB, -C, and -D and highlight the importance that the different strategies used by V. cholerae to regulate the RNA level of CsrB, -C, and -D confer the bacterium with a survival advantage.
霍乱弧菌是霍乱的病原体。有效的肠道定植是霍乱弧菌致病性和传播的关键步骤。在这项研究中，我们发现，缺失霍乱弧菌的 csrD 同源物会导致霍乱弧菌在成年小鼠肠道中的定植缺陷。通过分析 CsrB、CsrC 和 CsrD 的 RNA 水平，我们发现缺失会增加 CsrB 和 CsrD 的水平，但降低 CsrC 的水平。然而，缺失 CsrB 和 -D 不仅恢复了 缺失突变体的定植缺陷，而且还将 CsrC 恢复到野生型水平。这些结果表明，控制 CsrB、-C 和 -D 的 RNA 水平对于霍乱弧菌在成年小鼠中的定植至关重要。我们进一步证明，CsrB 和 CsrD 的 RNA 水平主要受 MshH 依赖性降解控制，而 CsrC 的水平主要由 CsrA 依赖性稳定决定。我们的数据表明，霍乱弧菌通过 MshH-CsrB/C/D-CsrA 调控途径，对 CsrB、-C 和 -D 的丰度进行差异化控制，从而精细调控 CsrA 靶标如 ToxR 的活性，使其更好地在成年小鼠肠道中存活。霍乱弧菌在肠道中的定植能力是其在宿主间适应性和传播性的关键因素。在这里，我们研究了霍乱弧菌在成年哺乳动物肠道定植的机制，发现 MshH 和 CsrA 精确控制 CsrB、-C 和 -D 的含量对霍乱弧菌在成年小鼠肠道中的定植起着至关重要的作用。这些数据扩展了我们对霍乱弧菌控制 CsrB、-C 和 -D 的 RNA 水平的机制的认识，并强调了霍乱弧菌使用不同策略来调节 CsrB、-C 和 -D 的 RNA 水平赋予其生存优势的重要性。
