Department of Microbiology and Environmental Toxicology, University of California - Santa Cruz, 1156 High St., BioMed 245, Santa Cruz, CA, 95064, USA.
Departments of Bioengineering, Chemistry and Biochemistry, California Nano Systems Institute, University of California - Los Angeles, 420 Westwood Plaza, Room 5121 Engineering V, Los Angeles, CA, 90095, USA.
Nat Commun. 2020 Mar 25;11(1):1549. doi: 10.1038/s41467-020-15331-8.
Biofilm formation by Vibrio cholerae facilitates environmental persistence, and hyperinfectivity within the host. Biofilm formation is regulated by 3',5'-cyclic diguanylate (c-di-GMP) and requires production of the type IV mannose-sensitive hemagglutinin (MSHA) pilus. Here, we show that the MSHA pilus is a dynamic extendable and retractable system, and its activity is directly controlled by c-di-GMP. The interaction between c-di-GMP and the ATPase MshE promotes pilus extension, whereas low levels of c-di-GMP correlate with enhanced retraction. Loss of retraction facilitated by the ATPase PilT increases near-surface roaming motility, and impairs initial surface attachment. However, prolonged retraction upon surface attachment results in reduced MSHA-mediated surface anchoring and increased levels of detachment. Our results indicate that c-di-GMP directly controls MshE activity, thus regulating MSHA pilus extension and retraction dynamics, and modulating V. cholerae surface attachment and colonization.
霍乱弧菌的生物膜形成有助于其在环境中的持久性和在宿主中的高感染力。生物膜的形成受 3'，5'-环二鸟苷酸（c-di-GMP）调控，需要产生 IV 型甘露糖敏感血凝素（MSHA）菌毛。在这里，我们表明 MSHA 菌毛是一个动态的可伸展和可缩回系统，其活性直接受 c-di-GMP 控制。c-di-GMP 与 ATP 酶 MshE 的相互作用促进菌毛延伸，而低水平的 c-di-GMP 与增强的缩回相关。ATP 酶 PilT 促进的缩回丧失增加了近表面漫游运动，并损害了初始表面附着。然而，表面附着后的长时间缩回导致 MSHA 介导的表面锚定减少和脱落水平增加。我们的结果表明，c-di-GMP 直接控制 MshE 活性，从而调节 MSHA 菌毛的延伸和缩回动力学，并调节霍乱弧菌的表面附着和定植。
