the flagellum of pseudomonas aeruginosa is required for resistance to clearance by surfactant protein a需要铜绿假单胞菌耐药性的鞭毛间隙通过表面活性剂的蛋白质.pdfVIP

The Flagellum of Pseudomonas aeruginosa Is Required for Resistance to Clearance by Surfactant Protein A 1 1 2 3 4 Shiping Zhang , Francis X. McCormack , Roger C. Levesque , George A. O’Toole , Gee W. Lau * 1 Division of Pulmonary and Critical Care Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America, 2 Centre de Recherche sur la Fonction Structure et Ingenierie des Proteines, Pavillon Charles-Eugene Marchand et Faculte de Medecine, Universite Laval, Ste- Foy, Quebec, Canada, 3 Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire, United States of America, 4 Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America Surfactant protein A (SP-A) is an important lung innate immune protein that kills microbial pathogens by opsonization and membrane permeabilization. We investigated the basis of SP-A-mediated pulmonary clearance of Pseudomonas aeruginosa using genetically-engineered SP-A mice and a library of signature-tagged P. aeruginosa mutants. A mutant with an insertion into flgE, the gene that encodes flagellar hook protein, was preferentially cleared by the SP-A+/+ mice, but survived in the SP- A2/ 2 mice. Opsonization by SP-A did not play a role in flgE clearance. However, exposure to SP-A directly permeabilized and killed the flgE mutant, but not the wild-type parental strain. P. aeruginosa strains with mutation in other flagellar genes, as well as mucoid, nonmotile isolates from cystic fibrosis patients, were also permeabilized by SP-A. Provision of the wild-type fliC gene restored the resistance to SP-A-mediated membrane permeabilization in the fliC-deficient bacteria. In addition, non- mucoid, motile revertants of CF isolates reacquired resistance to SP-A-mediated me