title: The ferrichrome receptor A as a new target for Pseudomonas aeruginosa virulence attenuation.
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.
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, 120-752, Korea Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 120-752, Korea.
authors.forename: Keehoon
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, 120-752, Korea.
authors.forename: Kang-Mu
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, 120-752, Korea Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 120-752, Korea.
authors.forename: Junhyeok
authors.initials: J
authors.lastname: Go
authors.affiliation: Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 120-752, Korea The Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, 120-752, Korea.
authors.forename: Jae-Chan
authors.initials: JC
authors.lastname: Ryu
authors.affiliation: Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 120-752, Korea The Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, 120-752, Korea.
authors.forename: Ji-Hwan
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, 120-752, Korea Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 120-752, Korea Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, 120-752, Korea sangsun_yoon@yuhs.ac.
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Yoon
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002228:Carbenicillin / Q000494:pharmacology; D004251:DNA Transposable Elements; D005291:Ferrichrome / Q000378:metabolism*; D015723:Gene Library; D007501:Iron / Q000378:metabolism; D008168:Lung / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000096:biosynthesis; D010196:Pancreatic Elastase / Q000096:biosynthesis; D010636:Phenols / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity*; D017384:Sequence Deletion; D013844:Thiazoles / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004251:DNA Transposable Elements; D009842:Oligopeptides; D010636:Phenols; D013844:Thiazoles; D037521:Virulence Factors; D005291:Ferrichrome; C025316:pyochelin; C042453:pyoverdin; D007501:Iron; D010196:Pancreatic Elastase; D002228:Carbenicillin
keywords: Pseudomonas aeruginosa; ferrichrome receptor A; virulence