Geisel School of Medicine
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-A(-/-) 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 membrane permeability. Resistance to SP-A was dependent on the presence of an intact flagellar structure, and independent of flagellar-dependent motility. We provide evidence that flagellar-deficient mutants harbor inadequate amounts of LPS required to resist membrane permeabilization by SP-A and cellular lysis by detergent targeting bacterial outer membranes. Thus, the flagellum of P. aeruginosa plays an indirect but important role resisting SP-A-mediated clearance and membrane permeabilization.
Zhang S, McCormack FX, Levesque RC, O'Toole GA, Lau GW. The flagellum of Pseudomonas aeruginosa is required for resistance to clearance by surfactant protein A. PLoS One. 2007 Jun 27;2(6):e564. doi: 10.1371/journal.pone.0000564. PMID: 17593964; PMCID: PMC1891440.
Dartmouth Digital Commons Citation
Zhang, Shiping; McCormack, Francis X.; Levesque, Roger C.; O'Toole, George A.; and Lau, Gee W., "The Flagellum of Pseudomonas aeruginosa Is Required for Resistance to Clearance by Surfactant Protein A" (2007). Dartmouth Scholarship. 1430.