c-di-GMP modulates type IV MSHA pilus retraction and surface attachment in Vibrio cholerae
Kyle A. Floyd, Calvin K. Lee, Wujing Xian, Mahmoud Nametalla, Aneesa Valentine, Benjamin Crair, Shiwei Zhu, Hannah Q. Hughes, Jennifer L. Chlebek, Daniel C. Wu, Jin Hwan Park, Ali M. Farhat, Charles J. Lomba, Courtney K. Ellison, Yves V. Brun, Javier Campos, Ankur B. Dalia, Jun Liu, Nicolas Biais, Gerard C. L. Wong, Fitnat H. Yildiz
Abstract
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.