The Pseudomonas aeruginosa flagellum confers resistance to pulmonary surfactant protein-A by impacting the production of exoproteases through quorum-sensing

Zhizhou Kuang, Yonghua Hao, Sunghei Hwang, Shiping Zhang, Eunice Kim, Henry T. Akinbi, Michael J. Schurr, Randall T. Irvin, Daniel J. Hassett, Gee Lau

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1220-1235
Number of pages16
JournalMolecular Microbiology
Volume79
Issue number5
DOIs
StatePublished - Mar 1 2011

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Pulmonary Surfactant-Associated Proteins
Exopeptidases
Pulmonary Surfactant-Associated Protein A
Quorum Sensing
Flagella
Pseudomonas aeruginosa
Bacteria
Lung
Proteins
Membranes
Muramidase
Virulence
Up-Regulation

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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The Pseudomonas aeruginosa flagellum confers resistance to pulmonary surfactant protein-A by impacting the production of exoproteases through quorum-sensing. / Kuang, Zhizhou; Hao, Yonghua; Hwang, Sunghei; Zhang, Shiping; Kim, Eunice; Akinbi, Henry T.; Schurr, Michael J.; Irvin, Randall T.; Hassett, Daniel J.; Lau, Gee.

In: Molecular Microbiology, Vol. 79, No. 5, 01.03.2011, p. 1220-1235.

Research output: Contribution to journalArticle

Kuang, Zhizhou ; Hao, Yonghua ; Hwang, Sunghei ; Zhang, Shiping ; Kim, Eunice ; Akinbi, Henry T. ; Schurr, Michael J. ; Irvin, Randall T. ; Hassett, Daniel J. ; Lau, Gee. / The Pseudomonas aeruginosa flagellum confers resistance to pulmonary surfactant protein-A by impacting the production of exoproteases through quorum-sensing. In: Molecular Microbiology. 2011 ; Vol. 79, No. 5. pp. 1220-1235.
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