This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takase, H.
Right arrow Articles by Otani, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takase, H.
Right arrow Articles by Otani, T.

 Previous Article  |  Next Article 

Infection and Immunity, April 2000, p. 1834-1839, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Impact of Siderophore Production on Pseudomonas aeruginosa Infections in Immunosuppressed Mice

Hiroyuki Takase,* Hironobu Nitanai, Kazuki Hoshino, and Tsuyoshi Otani

New Product Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Tokyo 134-8630, Japan

Received 11 October 1999/Returned for modification 29 November 1999/Accepted 3 January 2000

Pseudomonas aeruginosa produces siderophores, pyoverdin and pyochelin, for high-affinity iron uptake. To investigate their contribution to P. aeruginosa infections, we constructed allelic exchange mutants from strain PAO1 which were deficient in producing one or both of the siderophores. When inoculated into the calf muscles of immunosuppressed mice, pyochelin-deficient and pyoverdin-deficient mutants grew and killed the animals as efficiently as PAO1. In contrast, the pyochelin- and pyoverdin-deficient (double) mutant did not show lethal virulence, although it did infect the muscles. On the other hand, when inoculated intranasally, all mutants grew in the lungs and killed immunosuppressed mice. Compared with PAO1, however, the pyoverdin-deficient mutant and the double mutant grew poorly in the lungs, and the latter was significantly attenuated for virulence. Irrespective of the inoculation route, the pyoverdin-deficient and doubly deficient mutants detected in the blood were significantly less numerous than PAO1. Additionally, in vitro examination demonstrated that the growth of the double mutant was extremely reduced under a free-iron-restricted condition with apotransferrin but that the growth reduction was completely canceled by supplementation with hemoglobin as a heme source. These results suggest that both pyoverdin and pyochelin are required for efficient bacterial growth and full expression of virulence in P. aeruginosa infection, although pyoverdin may be comparatively more important for bacterial growth and dissemination. However, the siderophores were not always required for infection. It is possible that non-siderophore-mediated iron acquisition, such as via heme uptake, might also play an important role in P. aeruginosa infections.


* Corresponding author. Mailing address: New Product Research Laboratories I, Daiichi Pharmaceutical Co., Ltd. 16-13, Kita-Kasai 1-chome, Edogawa-ku, Tokyo 134-8630, Japan. Phone: 81-3-3680-0151. Fax: 81-3-5696-8344. E-mail: takas4px{at}daiichipharm.co.jp.


Infection and Immunity, April 2000, p. 1834-1839, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Reid, D. W., Anderson, G. J., Lamont, I. L. (2009). Role of lung iron in determining the bacterial and host struggle in cystic fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 297: L795-L802 [Abstract] [Full Text]  
  • Allard, K. A., Dao, J., Sanjeevaiah, P., McCoy-Simandle, K., Chatfield, C. H., Crumrine, D. S., Castignetti, D., Cianciotto, N. P. (2009). Purification of Legiobactin and Importance of This Siderophore in Lung Infection by Legionella pneumophila. Infect. Immun. 77: 2887-2895 [Abstract] [Full Text]  
  • O'May, C. Y., Sanderson, K., Roddam, L. F., Kirov, S. M., Reid, D. W. (2009). Iron-binding compounds impair Pseudomonas aeruginosa biofilm formation, especially under anaerobic conditions. J Med Microbiol 58: 765-773 [Abstract] [Full Text]  
  • Braud, A., Hannauer, M., Mislin, G. L. A., Schalk, I. J. (2009). The Pseudomonas aeruginosa Pyochelin-Iron Uptake Pathway and Its Metal Specificity. J. Bacteriol. 191: 3517-3525 [Abstract] [Full Text]  
  • Hoegy, F., Lee, X., Noel, S., Rognan, D., Mislin, G. L. A., Reimmann, C., Schalk, I. J. (2009). Stereospecificity of the Siderophore Pyochelin Outer Membrane Transporters in Fluorescent Pseudomonads. J. Biol. Chem. 284: 14949-14957 [Abstract] [Full Text]  
  • Clarke-Pearson, M. F., Brady, S. F. (2008). Paerucumarin, a New Metabolite Produced by the pvc Gene Cluster from Pseudomonas aeruginosa. J. Bacteriol. 190: 6927-6930 [Abstract] [Full Text]  
  • Spencer, M. R., Beare, P. A., Lamont, I. L. (2008). Role of Cell Surface Signaling in Proteolysis of an Alternative Sigma Factor in Pseudomonas aeruginosa. J. Bacteriol. 190: 4865-4869 [Abstract] [Full Text]  
  • Miranda-CasoLuengo, R., Prescott, J. F., Vazquez-Boland, J. A., Meijer, W. G. (2008). The Intracellular Pathogen Rhodococcus equi Produces a Catecholate Siderophore Required for Saprophytic Growth. J. Bacteriol. 190: 1631-1637 [Abstract] [Full Text]  
  • Greenwald, J., Hoegy, F., Nader, M., Journet, L., Mislin, G. L. A., Graumann, P. L., Schalk, I. J. (2007). Real Time Fluorescent Resonance Energy Transfer Visualization of Ferric Pyoverdine Uptake in Pseudomonas aeruginosa: A ROLE FOR FERROUS IRON. J. Biol. Chem. 282: 2987-2995 [Abstract] [Full Text]  
  • O Cuiv, P., Keogh, D., Clarke, P., O'Connell, M. (2007). FoxB of Pseudomonas aeruginosa Functions in the Utilization of the Xenosiderophores Ferrichrome, Ferrioxamine B, and Schizokinen: Evidence for Transport Redundancy at the Inner Membrane. J. Bacteriol. 189: 284-287 [Abstract] [Full Text]  
  • Ge, L., Seah, S. Y. K. (2006). Heterologous Expression, Purification, and Characterization of an L-Ornithine N5-Hydroxylase Involved in Pyoverdine Siderophore Biosynthesis in Pseudomonas aeruginosa.. J. Bacteriol. 188: 7205-7210 [Abstract] [Full Text]  
  • Oide, S., Moeder, W., Krasnoff, S., Gibson, D., Haas, H., Yoshioka, K., Turgeon, B. G. (2006). NPS6, Encoding a Nonribosomal Peptide Synthetase Involved in Siderophore-Mediated Iron Metabolism, Is a Conserved Virulence Determinant of Plant Pathogenic Ascomycetes. Plant Cell 18: 2836-2853 [Abstract] [Full Text]  
  • McPhee, J. B., Bains, M., Winsor, G., Lewenza, S., Kwasnicka, A., Brazas, M. D., Brinkman, F. S. L., Hancock, R. E. W. (2006). Contribution of the PhoP-PhoQ and PmrA-PmrB Two-Component Regulatory Systems to Mg2+-Induced Gene Regulation in Pseudomonas aeruginosa. J. Bacteriol. 188: 3995-4006 [Abstract] [Full Text]  
  • Lamont, I. L., Martin, L. W., Sims, T., Scott, A., Wallace, M. (2006). Characterization of a Gene Encoding an Acetylase Required for Pyoverdine Synthesis in Pseudomonas aeruginosa.. J. Bacteriol. 188: 3149-3152 [Abstract] [Full Text]  
  • Speziali, C. D., Dale, S. E., Henderson, J. A., Vines, E. D., Heinrichs, D. E. (2006). Requirement of Staphylococcus aureus ATP-Binding Cassette-ATPase FhuC for Iron-Restricted Growth and Evidence that It Functions with More than One Iron Transporter. J. Bacteriol. 188: 2048-2055 [Abstract] [Full Text]  
  • Hissen, A. H. T., Wan, A. N. C., Warwas, M. L., Pinto, L. J., Moore, M. M. (2005). The Aspergillus fumigatus Siderophore Biosynthetic Gene sidA, Encoding L-Ornithine N5-Oxygenase, Is Required for Virulence. Infect. Immun. 73: 5493-5503 [Abstract] [Full Text]  
  • Sadikot, R. T., Blackwell, T. S., Christman, J. W., Prince, A. S. (2005). Pathogen-Host Interactions in Pseudomonas aeruginosa Pneumonia. Am. J. Respir. Crit. Care Med. 171: 1209-1223 [Abstract] [Full Text]  
  • Hoegy, F., Celia, H., Mislin, G. L., Vincent, M., Gallay, J., Schalk, I. J. (2005). Binding of Iron-free Siderophore, a Common Feature of Siderophore Outer Membrane Transporters of Escherichia coli and Pseudomonas aeruginosa. J. Biol. Chem. 280: 20222-20230 [Abstract] [Full Text]  
  • Miranda-CasoLuengo, R., Duffy, P. S., O'Connell, E. P., Graham, B. J., Mangan, M. W., Prescott, J. F., Meijer, W. G. (2005). The Iron-Regulated iupABC Operon Is Required for Saprophytic Growth of the Intracellular Pathogen Rhodococcus equi at Low Iron Concentrations. J. Bacteriol. 187: 3438-3444 [Abstract] [Full Text]  
  • Szczepanowski, R., Braun, S., Riedel, V., Schneiker, S., Krahn, I., Puhler, A., Schluter, A. (2005). The 120 592 bp IncF plasmid pRSB107 isolated from a sewage-treatment plant encodes nine different antibiotic-resistance determinants, two iron-acquisition systems and other putative virulence-associated functions. Microbiology 151: 1095-1111 [Abstract] [Full Text]  
  • Smith, E. E., Sims, E. H., Spencer, D. H., Kaul, R., Olson, M. V. (2005). Evidence for Diversifying Selection at the Pyoverdine Locus of Pseudomonas aeruginosa. J. Bacteriol. 187: 2138-2147 [Abstract] [Full Text]  
  • Ong, C., Ooi, C. H., Wang, D., Chong, H., Ng, K. C., Rodrigues, F., Lee, M. A., Tan, P. (2004). Patterns of large-scale genomic variation in virulent and avirulent Burkholderia species. Genome Res 14: 2295-2307 [Abstract] [Full Text]  
  • Reimmann, C., Patel, H. M., Walsh, C. T., Haas, D. (2004). PchC Thioesterase Optimizes Nonribosomal Biosynthesis of the Peptide Siderophore Pyochelin in Pseudomonas aeruginosa. J. Bacteriol. 186: 6367-6373 [Abstract] [Full Text]  
  • Frisk, A., Schurr, J. R., Wang, G., Bertucci, D. C., Marrero, L., Hwang, S. H., Hassett, D. J., Schurr, M. J. (2004). Transcriptome Analysis of Pseudomonas aeruginosa after Interaction with Human Airway Epithelial Cells. Infect. Immun. 72: 5433-5438 [Abstract] [Full Text]  
  • Vandenende, C. S., Vlasschaert, M., Seah, S. Y. K. (2004). Functional Characterization of an Aminotransferase Required for Pyoverdine Siderophore Biosynthesis in Pseudomonas aeruginosa PAO1. J. Bacteriol. 186: 5596-5602 [Abstract] [Full Text]  
  • Huston, W. M., Potter, A. J., Jennings, M. P., Rello, J., Hauser, A. R., McEwan, A. G. (2004). Survey of Ferroxidase Expression and Siderophore Production in Clinical Isolates of Pseudomonas aeruginosa. J. Clin. Microbiol. 42: 2806-2809 [Abstract] [Full Text]  
  • Ghysels, B., Dieu, B. T. M., Beatson, S. A., Pirnay, J.-P., Ochsner, U. A., Vasil, M. L., Cornelis, P. (2004). FpvB, an alternative type I ferripyoverdine receptor of Pseudomonas aeruginosa. Microbiology 150: 1671-1680 [Abstract] [Full Text]  
  • O Cuiv, P., Clarke, P., Lynch, D., O'Connell, M. (2004). Identification of rhtX and fptX, Novel Genes Encoding Proteins That Show Homology and Function in the Utilization of the Siderophores Rhizobactin 1021 by Sinorhizobium meliloti and Pyochelin by Pseudomonas aeruginosa, Respectively. J. Bacteriol. 186: 2996-3005 [Abstract] [Full Text]  
  • Visser, M. B., Majumdar, S., Hani, E., Sokol, P. A. (2004). Importance of the Ornibactin and Pyochelin Siderophore Transport Systems in Burkholderia cenocepacia Lung Infections. Infect. Immun. 72: 2850-2857 [Abstract] [Full Text]  
  • Barekzi, N., Joshi, S., Irwin, S., Ontl, T., Schweizer, H. P. (2004). Genetic characterization of pcpS, encoding the multifunctional phosphopantetheinyl transferase of Pseudomonas aeruginosa. Microbiology 150: 795-803 [Abstract] [Full Text]  
  • Hissen, A. H. T., Chow, J. M. T., Pinto, L. J., Moore, M. M. (2004). Survival of Aspergillus fumigatus in Serum Involves Removal of Iron from Transferrin: the Role of Siderophores. Infect. Immun. 72: 1402-1408 [Abstract] [Full Text]  
  • Ackerley, D. F., Caradoc-Davies, T. T., Lamont, I. L. (2003). Substrate Specificity of the Nonribosomal Peptide Synthetase PvdD from Pseudomonas aeruginosa. J. Bacteriol. 185: 2848-2855 [Abstract] [Full Text]  
  • de Chial, M., Ghysels, B., Beatson, S. A., Geoffroy, V., Meyer, J. M., Pattery, T., Baysse, C., Chablain, P., Parsons, Y. N., Winstanley, C., Cordwell, S. J., Cornelis, P. (2003). Identification of type II and type III pyoverdine receptors from Pseudomonas aeruginosa. Microbiology 149: 821-831 [Abstract] [Full Text]  
  • Redly, G. A., Poole, K. (2003). Pyoverdine-Mediated Regulation of FpvA Synthesis in Pseudomonas aeruginosa: Involvement of a Probable Extracytoplasmic-Function Sigma Factor, FpvI. J. Bacteriol. 185: 1261-1265 [Abstract] [Full Text]  
  • Finking, R., Solsbacher, J., Konz, D., Schobert, M., Schafer, A., Jahn, D., Marahiel, M. A. (2002). Characterization of a New Type of Phosphopantetheinyl Transferase for Fatty Acid and Siderophore Synthesis in Pseudomonas aeruginosa. J. Biol. Chem. 277: 50293-50302 [Abstract] [Full Text]  
  • Shen, J., Meldrum, A., Poole, K. (2002). FpvA Receptor Involvement in Pyoverdine Biosynthesis in Pseudomonas aeruginosa. J. Bacteriol. 184: 3268-3275 [Abstract] [Full Text]  
  • Lamont, I. L., Beare, P. A., Ochsner, U., Vasil, A. I., Vasil, M. L. (2002). Siderophore-mediated signaling regulates virulence factor production in Pseudomonasaeruginosa. Proc. Natl. Acad. Sci. USA 99: 7072-7077 [Abstract] [Full Text]  
  • Reimmann, C., Patel, H. M., Serino, L., Barone, M., Walsh, C. T., Haas, D. (2001). Essential PchG-Dependent Reduction in Pyochelin Biosynthesis of Pseudomonas aeruginosa. J. Bacteriol. 183: 813-820 [Abstract] [Full Text]