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 language | English (US) |
|---|---|
| Pages (from-to) | 1220-1235 |
| Number of pages | 16 |
| Journal | Molecular Microbiology |
| Volume | 79 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 1 2011 |
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ASJC Scopus subject areas
- Microbiology
- Molecular Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - The Pseudomonas aeruginosa flagellum confers resistance to pulmonary surfactant protein-A by impacting the production of exoproteases through quorum-sensing
AU - Kuang, Zhizhou
AU - Hao, Yonghua
AU - Hwang, Sunghei
AU - Zhang, Shiping
AU - Kim, Eunice
AU - Akinbi, Henry T.
AU - Schurr, Michael J.
AU - Irvin, Randall T.
AU - Hassett, Daniel J.
AU - Lau, Gee
PY - 2011/3/1
Y1 - 2011/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79951782204&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951782204&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2958.2010.07516.x
DO - 10.1111/j.1365-2958.2010.07516.x
M3 - Article
C2 - 21205009
AN - SCOPUS:79951782204
VL - 79
SP - 1220
EP - 1235
JO - Molecular Microbiology
JF - Molecular Microbiology
SN - 0950-382X
IS - 5
ER -