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

• Published in: FEMS microbiology letters Vol. 363; no. 11; p. fnw104
• Main Authors: Lee, Keehoon, Lee, Kang-Mu, Go, Junhyeok, Ryu, Jae-Chan, Ryu, Ji-Hwan, Yoon, Sang Sun
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.06.2016
• Subjects: Animals; Antibiotics; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - metabolism; Biofilms; Biofilms - drug effects; Biofilms - growth & development; Carbenicillin - pharmacology; DNA Transposable Elements; Ferrichrome - metabolism; Gene Library; Iron - metabolism; Lung - microbiology; Mice; Microbial Sensitivity Tests; Microbiology; Oligopeptides - biosynthesis; Pancreatic Elastase - biosynthesis; Pathogens; Phenols - metabolism; Pseudomonas aeruginosa - chemistry; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - pathogenicity; Sequence Deletion; Thiazoles - metabolism; Virulence Factors - genetics; Virulence Factors - metabolism; virulence; ferrichrome receptor A; Pseudomonas aeruginosa
• ISSN: 1574-6968; 0378-1097; 1574-6968
• DOI: 10.1093/femsle/fnw104

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. Antibiotics stimulate biofilm formation in P. aeruginosa for reasons to be further explored. A mutant of ferrichrome receptor A was defective in antibiotic-inducible biofilm formation and exhibited concomitant virulence attenuation.