Abstract
Pseudomonasaeruginosa(PA) is a Gram-negative bacterial pathogen commonly associated with chronic lung infections. Previously, we have identified several PA virulence factors that are important for resistance to the surfactant protein-A (SP-A), a pulmonary innate immunity protein that mediates bacterial opsonization and membrane permeabilization. In this study, we demonstrate that the type IV pilus (Tfp) is important in the resistance of PA to the antibacterial effects of SP-A. The Tfp-deficient mutant ΔpilA is severely attenuated in an acute pneumonia model of infection in the lungs of wild-type mice, but is virulent in the lungs of SP-A-/- mice. The ΔpilA bacteria are more susceptible to SP-A-mediated aggregation and opsonization. In addition, the integrity of the outer membranes of ΔpilA bacteria is compromised, rendering them more susceptible to SP-A-mediated membrane permeabilization. By comparing Tfp extension and retraction mutants, we demonstrate that the increased susceptibility of ΔpilA to SP-A-mediated opsonization requires the total absence of Tfp from PA cells. Finally, we provide evidence of increased expression of nonpilus adhesin OprH that may serve as an SP-A ligand, resulting in increased phagocytosis and preferential pulmonary clearance of ΔpilA.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 227-239 |
| Number of pages | 13 |
| Journal | Journal of Innate Immunity |
| Volume | 6 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2014 |
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Keywords
- Adhesins
- Membrane permeabilization
- Opsonization
- Pseudomonas aeruginosa
- Surfactant protein-A
- Type IV pilus
ASJC Scopus subject areas
- Immunology and Allergy
Cite this
Type iv pilus of pseudomonasaeruginosa confers resistance to antimicrobial activities of the pulmonary surfactant protein-a. / Tan, Rommel Max; Kuang, Zhizhou; Hao, Yonghua; Lau, Gee W.
In: Journal of Innate Immunity, Vol. 6, No. 2, 02.2014, p. 227-239.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Type iv pilus of pseudomonasaeruginosa confers resistance to antimicrobial activities of the pulmonary surfactant protein-a
AU - Tan, Rommel Max
AU - Kuang, Zhizhou
AU - Hao, Yonghua
AU - Lau, Gee W.
PY - 2014/2
Y1 - 2014/2
N2 - Pseudomonasaeruginosa(PA) is a Gram-negative bacterial pathogen commonly associated with chronic lung infections. Previously, we have identified several PA virulence factors that are important for resistance to the surfactant protein-A (SP-A), a pulmonary innate immunity protein that mediates bacterial opsonization and membrane permeabilization. In this study, we demonstrate that the type IV pilus (Tfp) is important in the resistance of PA to the antibacterial effects of SP-A. The Tfp-deficient mutant ΔpilA is severely attenuated in an acute pneumonia model of infection in the lungs of wild-type mice, but is virulent in the lungs of SP-A-/- mice. The ΔpilA bacteria are more susceptible to SP-A-mediated aggregation and opsonization. In addition, the integrity of the outer membranes of ΔpilA bacteria is compromised, rendering them more susceptible to SP-A-mediated membrane permeabilization. By comparing Tfp extension and retraction mutants, we demonstrate that the increased susceptibility of ΔpilA to SP-A-mediated opsonization requires the total absence of Tfp from PA cells. Finally, we provide evidence of increased expression of nonpilus adhesin OprH that may serve as an SP-A ligand, resulting in increased phagocytosis and preferential pulmonary clearance of ΔpilA.
AB - Pseudomonasaeruginosa(PA) is a Gram-negative bacterial pathogen commonly associated with chronic lung infections. Previously, we have identified several PA virulence factors that are important for resistance to the surfactant protein-A (SP-A), a pulmonary innate immunity protein that mediates bacterial opsonization and membrane permeabilization. In this study, we demonstrate that the type IV pilus (Tfp) is important in the resistance of PA to the antibacterial effects of SP-A. The Tfp-deficient mutant ΔpilA is severely attenuated in an acute pneumonia model of infection in the lungs of wild-type mice, but is virulent in the lungs of SP-A-/- mice. The ΔpilA bacteria are more susceptible to SP-A-mediated aggregation and opsonization. In addition, the integrity of the outer membranes of ΔpilA bacteria is compromised, rendering them more susceptible to SP-A-mediated membrane permeabilization. By comparing Tfp extension and retraction mutants, we demonstrate that the increased susceptibility of ΔpilA to SP-A-mediated opsonization requires the total absence of Tfp from PA cells. Finally, we provide evidence of increased expression of nonpilus adhesin OprH that may serve as an SP-A ligand, resulting in increased phagocytosis and preferential pulmonary clearance of ΔpilA.
KW - Adhesins
KW - Membrane permeabilization
KW - Opsonization
KW - Pseudomonas aeruginosa
KW - Surfactant protein-A
KW - Type IV pilus
UR - http://www.scopus.com/inward/record.url?scp=84896375051&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896375051&partnerID=8YFLogxK
U2 - 10.1159/000354304
DO - 10.1159/000354304
M3 - Article
C2 - 24080545
AN - SCOPUS:84896375051
VL - 6
SP - 227
EP - 239
JO - Journal of Innate Immunity
JF - Journal of Innate Immunity
SN - 1662-811X
IS - 2
ER -