Role of iron uptake systems in pseudomonas aeruginosa virulence and airway infection

Fabrizia Minandri, Francesco Imperi, Emanuela Frangipani, Carlo Bonchi, Daniela Visaggio, Marcella Facchini, Paolo Pasquali, Alessandra Bragonzi, Paolo Visca

Research output: Contribution to journalArticle

Abstract

Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and chronic lung infections in cystic fibrosis patients.Iron is essential for bacterial growth, and P. aeruginosa expresses multiple iron uptake systems, whose role in lung infectiondeserves further investigation. P. aeruginosa Fe3+ uptake systems include the pyoverdine and pyochelin siderophores andtwo systems for heme uptake, all of which are dependent on the TonB energy transducer. P. aeruginosa also has the FeoB transporterfor Fe2+ acquisition. To assess the roles of individual iron uptake systems in P. aeruginosa lung infection, single and doubledeletion mutants were generated in P. aeruginosa PAO1 and characterized in vitro, using iron-poor media and human serum,and in vivo, using a mouse model of lung infection. The iron uptake-null mutant (tonB1 feoB) and the Fe3+ transportmutant (tonB1) did not grow aerobically under low-iron conditions and were avirulent in the mouse model. Conversely, the wildtype and the feoB, hasR phuR (heme uptake), and pchD (pyochelin) mutants grew in vitro and caused 60 to 90% mortality inmice. The pyoverdine mutant (pvdA) and the siderophore-null mutant (pvdA pchD) grew aerobically in iron-poor media but notin human serum, and they caused low mortality in mice (10 to 20%). To differentiate the roles of pyoverdine in iron uptake andvirulence regulation, a pvdA fpvR double mutant defective in pyoverdine production but expressing wild-type levels of pyoverdine-regulated virulence factors was generated. Deletion of fpvR in the pvdA background partially restored the lethal phenotype,indicating that pyoverdine contributes to the pathogenesis of P. aeruginosa lung infection by combining iron transport and virulence-inducing capabilities.

Original languageEnglish
Pages (from-to)2324-2335
Number of pages12
JournalInfection and Immunity
Volume84
Issue number8
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

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  • Cite this

    Minandri, F., Imperi, F., Frangipani, E., Bonchi, C., Visaggio, D., Facchini, M., Pasquali, P., Bragonzi, A., & Visca, P. (2016). Role of iron uptake systems in pseudomonas aeruginosa virulence and airway infection. Infection and Immunity, 84(8), 2324-2335. https://doi.org/10.1128/IAI.00098-16