complex c-di-gmp signaling networks mediate transition between virulence properties and biofilm formation in salmonella enterica serovar typhimurium复杂c-di-gmp信号网络调解之间的过渡毒性在鼠伤寒沙门氏菌血清型属性和生物膜的形成.pdf

Complex c-di-GMP Signaling Networks Mediate Transition between Virulence Properties and Biofilm Formation in Salmonella enterica Serovar Typhimurium 1. 1. 1 1 2 Irfan Ahmad , Agaristi Lamprokostopoulou , Soazig Le Guyon , Elena Streck , Melanie Barthel , 1 2 ¨ 1 Verena Peters , Wolf-Dieter Hardt , Ute Romling * ¨ ¨ 1 Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden, 2 Institute of Microbiology, ETH Zurich, Zurich, Switzerland Abstract Upon Salmonella enterica serovar Typhimurium infection of the gut, an early line of defense is the gastrointestinal epithelium which senses the pathogen and intrusion along the epithelial barrier is one of the first events towards disease. Recently, we showed that high intracellular amounts of the secondary messenger c-di-GMP in S. typhimurium inhibited invasion and abolished induction of a pro-inflammatory immune response in the colonic epithelial cell line HT-29 suggesting regulation of transition between biofilm formation and virulence by c-di-GMP in the intestine. Here we show that highly complex c-di-GMP signaling networks consisting of distinct groups of c-di-GMP synthesizing and degrading proteins modulate the virulence phenotypes invasion, IL-8 production and in vivo colonization in the streptomycin-treated mouse model implying a spatial and timely modulation of