title: The Pseudomonas aeruginosa flagellum confers resistance to pulmonary surfactant protein-A by impacting the production of exoproteases through quorum-sensing.
abstract: Surfactant protein-A (SP-A) is an important antimicrobial protein that opsonizes and permeabilizes membranes of microbial pathogens in mammalian lungs. Previously, we have shown that Pseudomonas aeruginosa flagellum-deficient mutants are preferentially cleared in the lungs of wild-type mice by SP-A-mediated membrane permeabilization, and not by opsonization. In this study, we report a flagellum-mediated mechanism of P. aeruginosa resistance to SP-A. We discovered that flagellum-deficient (ΔfliC) bacteria are unable to produce adequate amounts of exoproteases to degrade SP-A in vitro and in vivo, leading to its preferential clearance in the lungs of SP-A(+/+) mice. In addition, ΔfliC bacteria failed to degrade another important lung antimicrobial protein lysozyme. Detailed analyses showed that ΔfliC bacteria are unable to upregulate the transcription of lasI and rhlI genes, impairing the production of homoserine lactones necessary for quorum-sensing, an important virulence process that regulates the production of multiple exoproteases. Thus, reduced ability of ΔfliC bacteria to quorum-sense attenuates production of exoproteases and limits degradation of SP-A, thereby conferring susceptibility to this major pulmonary host defence protein.
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Kuang
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Hao
authors.forename: Sunghei
authors.initials: S
authors.lastname: Hwang
authors.forename: Shiping
authors.initials: S
authors.lastname: Zhang
authors.forename: Eunice
authors.initials: E
authors.lastname: Kim
authors.forename: Henry T
authors.initials: HT
authors.lastname: Akinbi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schurr
authors.forename: Randall T
authors.initials: RT
authors.lastname: Irvin
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hassett
authors.forename: Gee W
authors.initials: GW
authors.lastname: Lau
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D020689:Exopeptidases / Q000235:genetics / Q000276:immunology*; D005260:Female; D005407:Flagella / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000276:immunology*; D053038:Quorum Sensing
chemical_list: D001426:Bacterial Proteins; D037662:Pulmonary Surfactant-Associated Protein A; D020689:Exopeptidases