yfibnr mediates cyclic di-gmp dependent small colony variant formation and persistence in pseudomonas aeruginosayfibnr介导循环di-gmp依赖小殖民地变体以铜绿假单胞菌形成和持久性.pdfVIP

YfiBNR Mediates Cyclic di-GMP Dependent Small Colony Variant Formation and Persistence in Pseudomonas aeruginosa 1 1 2 3 1 ´ 1 Jacob G. Malone *, Tina Jaeger , Christian Spangler , Daniel Ritz , Anne Spang , Cecile Arrieumerlou , 2 4 1 Volkhard Kaever , Regine Landmann , Urs Jenal * 1 Biozentrum, University of Basel, Basel, Switzerland, 2 Institute of Pharmacology, Hannover Medical School, Hannover, Germany, 3 Actelion Pharmaceuticals Ltd., Allschwil, Switzerland, 4 Department of Biomedicine, University Hospital, Basel, Switzerland Abstract During long-term cystic fibrosis lung infections, Pseudomonas aeruginosa undergoes genetic adaptation resulting in progressively increased persistence and the generation of adaptive colony morphotypes. This includes small colony variants (SCVs), auto-aggregative, hyper-adherent cells whose appearance correlates with poor lung function and persistence of infection. The SCV morphotype is strongly linked to elevated levels of cyclic-di-GMP, a ubiquitous bacterial second messenger that regulates the transition between motile and sessile, cooperative lifestyles. A genetic screen in PA01 for SCV- related loci identified the yfiBNR operon, encoding a tripartite signaling module that regulates c-di-GMP levels in P. aeruginosa. Subsequent analysis determined that YfiN is a membrane-integral diguanylate cyclase whose activity is tightly controlled by YfiR, a small periplasmic protein, and the OmpA/Pal-like outer-membrane lipoprotein YfiB. Exopolysaccharide synthesis was identified as the principal downstream