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The ferrichrome receptor A as a new target for Pseudomonas aeruginosa virulence attenuation

Authors
 Keehoon Lee  ;  Kang-Mu Lee  ;  Junhyeok Go  ;  Jae-Chan Ryu  ;  Ji-Hwan Ryu  ;  Sang Sun Yoon 
Citation
 FEMS Microbiology Letters, Vol.363(11) : 104, 2016 
Journal Title
 FEMS Microbiology Letters 
ISSN
 0378-1097 
Issue Date
2016
MeSH
Animals ; Bacterial Outer Membrane Proteins/genetics* ; Bacterial Outer Membrane Proteins/metabolism ; Biofilms/drug effects ; Biofilms/growth & development ; Carbenicillin/pharmacology ; DNA Transposable Elements ; Ferrichrome/metabolism* ; Gene Library ; Iron/metabolism ; Lung/microbiology ; Mice ; Microbial Sensitivity Tests ; Oligopeptides/biosynthesis ; Pancreatic Elastase/biosynthesis ; Phenols/metabolism ; Pseudomonas aeruginosa/chemistry ; Pseudomonas aeruginosa/genetics ; Pseudomonas aeruginosa/pathogenicity* ; Sequence Deletion ; Thiazoles/metabolism ; Virulence Factors/genetics* ; Virulence Factors/metabolism
Keywords
Pseudomonas aeruginosa ; ferrichrome receptor A ; virulence
Abstract
Pseudomonas aeruginosa is an opportunistic pathogen, known to develop robust biofilms. Its biofilm development increases when antibiotics are presented at subminimal inhibitory concentrations (MICs) for reasons that remain unclear. In order to identify genes that affect biofilm development under such a sublethal antibiotic stress condition, we screened a transposon (Tn) mutant library of PAO1, a prototype P. aeruginosa strain. Among ∼5000 mutants, a fiuA gene mutant was verified to form very defective biofilms in the presence of sub-MIC carbenicillin. The fiuA gene encodes ferrichrome receptor A, involved in the iron acquisition process. Of note, biofilm formation was not decreased in the ΔpchΔpvd mutant defective in the production of pyochelin and pyoverdine, two well-characterized P. aeruginosa siderophore molecules. Moreover, ΔfiuA, a non-polar fiuA deletion mutant, produced a significantly decreased level of elastase, a major virulence determinant. Mouse airway infection experiments revealed that the mutant expressed significantly less pathogenicity. Our results suggest that the fiuA gene has pleiotropic functions that affect P. aeruginosa biofilm development and virulence. The targeting of FiuA could enable the attenuation of P. aeruginosa virulence and may be suitable for the development of a drug that specifically controls the virulence of this important pathogen.
Files in This Item:
T201601486.pdf Download
DOI
10.1093/femsle/fnw104
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Ryu, Ji Hwan(유지환)
Yoon, Sang Sun(윤상선) ORCID logo https://orcid.org/0000-0003-2979-365X
Lee, Kang Mu(이강무) ORCID logo https://orcid.org/0000-0001-7414-5921
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146856
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