Cyclic-di-GMP is required for corneal infection by Pseudomonas aeruginosa and modulates host immunity
Research output: Working paper › Preprint › Research
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Cyclic-di-GMP is required for corneal infection by Pseudomonas aeruginosa and modulates host immunity. / Hoong Yam, J.K.; Aung, T.T.; Chua, S.L.; Cheng, Y.; Kohli, G.S.; Zhou, J.; Constancias, F.; Liu, Y.; Cai, Z.; Santillan Salido, M.M.; Drautz-Moses, D.I.; Rice, S.A.; Schuster, S.C.; Wu, B.; Kjelleberg, S.; Tolker-Nielsen, T.; Beuerman, R.W.; Givskov, M.; Yang, L.
bioRxiv, 2017.Research output: Working paper › Preprint › Research
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TY - UNPB
T1 - Cyclic-di-GMP is required for corneal infection by Pseudomonas aeruginosa and modulates host immunity
AU - Hoong Yam, J.K.
AU - Aung, T.T.
AU - Chua, S.L.
AU - Cheng, Y.
AU - Kohli, G.S.
AU - Zhou, J.
AU - Constancias, F.
AU - Liu, Y.
AU - Cai, Z.
AU - Santillan Salido, M.M.
AU - Drautz-Moses, D.I.
AU - Rice, S.A.
AU - Schuster, S.C.
AU - Wu, B.
AU - Kjelleberg, S.
AU - Tolker-Nielsen, T.
AU - Beuerman, R.W.
AU - Givskov, M.
AU - Yang, L.
PY - 2017
Y1 - 2017
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.
AB - 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.
U2 - 10.1101/098749
DO - 10.1101/098749
M3 - Preprint
BT - Cyclic-di-GMP is required for corneal infection by Pseudomonas aeruginosa and modulates host immunity
PB - bioRxiv
ER -
ID: 340400086