Pseudomonas aeruginosa Elastase provides an Escape from phagocytosis by degrading the pulmonary surfactant protein-A

Zhizhou Kuang, Yonghua Hao, Brent E. Walling, Jayme L. Jeffries, Dennis E. Ohman, Gee W. Lau

Research output: Contribution to journalArticle

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute pneumonitis in immunocompromised patients and chronic lung infections in individuals with cystic fibrosis and other bronchiectasis. Over 75% of clinical isolates of P. aeruginosa secrete elastase B (LasB), an elastolytic metalloproteinase that is encoded by the lasB gene. Previously, in vitro studies have demonstrated that LasB degrades a number of components in both the innate and adaptive immune systems. These include surfactant proteins, antibacterial peptides, cytokines, chemokines and immunoglobulins. However, the contribution of LasB to lung infection by P. aeruginosa and to inactivation of pulmonary innate immunity in vivo needs more clarification. In this study, we examined the mechanisms underlying enhanced clearance of the ΔlasB mutant in mouse lungs. The ΔlasB mutant was attenuated in virulence when compared to the wild-type strain PAO1 during lung infection in SP-A+/+ mice. However, the ΔlasB mutant was as virulent as PAO1 in the lungs of SP-A-/- mice. Detailed analysis showed that the ΔlasB mutant was more susceptible to SP-A-mediated opsonization but not membrane permeabilization. In vitro and in vivo phagocytosis experiments revealed that SP-A augmented the phagocytosis of ΔlasB mutant bacteria more efficiently than the isogenic wild-type PAO1. The ΔlasB mutant was found to have a severely reduced ability to degrade SP-A, consequently making it unable to evade opsonization by the collectin during phagocytosis. These results suggest that P. aeruginosa LasB protects against SP-A-mediated opsonization by degrading the collectin.

Original languageEnglish (US)
Article numbere27091
JournalPloS one
Volume6
Issue number11
DOIs
StatePublished - Nov 1 2011

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Pulmonary Surfactant-Associated Proteins
Collectins
Pulmonary Surfactant-Associated Protein A
elastase
phagocytosis
Phagocytosis
Pseudomonas aeruginosa
surfactants
lungs
Lung
mutants
Immune system
Pancreatic Elastase
Metalloproteases
Pathogens
Chemokines
Surface-Active Agents
Immunoglobulins
Bacteria
proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Pseudomonas aeruginosa Elastase provides an Escape from phagocytosis by degrading the pulmonary surfactant protein-A. / Kuang, Zhizhou; Hao, Yonghua; Walling, Brent E.; Jeffries, Jayme L.; Ohman, Dennis E.; Lau, Gee W.

In: PloS one, Vol. 6, No. 11, e27091, 01.11.2011.

Research output: Contribution to journalArticle

Kuang, Zhizhou ; Hao, Yonghua ; Walling, Brent E. ; Jeffries, Jayme L. ; Ohman, Dennis E. ; Lau, Gee W. / Pseudomonas aeruginosa Elastase provides an Escape from phagocytosis by degrading the pulmonary surfactant protein-A. In: PloS one. 2011 ; Vol. 6, No. 11.
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