TY - JOUR T1 - Cyclic-di-GMP is required for corneal infection by <em>Pseudomonas aeruginosa</em> and modulates host immunity JF - bioRxiv DO - 10.1101/098749 SP - 098749 AU - Joey Kuok Hoong Yam AU - Thet Tun Aung AU - Song Lin Chua AU - Yingying Cheng AU - Gurjeet Singh Kohli AU - Jianuan Zhou AU - Florentin Constancias AU - Yang Liu AU - Zhao Cai AU - May Margarette Santillan Salido AU - Daniela I. Drautz-Moses AU - Scott A. Rice AU - Stephan Christoph Schuster AU - Bin Wu AU - Staffan Kjelleberg AU - Tim Tolker-Nielsen AU - Roger W. Beuerman AU - Michael Givskov AU - Liang Yang Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/01/06/098749.abstract N2 - Biofilms are extremely tolerant toward antimicrobial treatment and host immune clearance due to their distinct physiology and protection by extracellular polymeric substances. Bis-(3´-5´)-cyclic dimeric guanosine monophosphate (c-di-GMP) is an essential messenger that regulates biofilm formation by a wide range of bacteria. However, there is a lack of physiological characterization of biofilms in vivo as well as the roles of c-di-GMP signaling in mediating host-biofilm interactions. Here, we employed dual RNA-Seq to characterize the host and pathogen transcriptomes during Pseudomonas aeruginosa infection using a mouse keratitis model. In vivo P. aeruginosa biofilms maintained a distinct physiology compared with in vitro P. aeruginosa biofilms, with enhanced virulence and iron uptake capacity. C-di-GMP synthesis was enhanced in P. aeruginosa cells in vivo, potentially due to down-regulation of the expression of several phosphodiesterases (e.g., DipA, NbdA). Increased intracellular c-di-GMP levels were required for long-term ocular colonization of P. aeruginosa and impaired host innate immunity. ER -