1887

Abstract

Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and species-specific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.000220
2016-02-01
2022-01-18
Loading full text...

Full text loading...

/deliver/fulltext/micro/162/2/191.html?itemId=/content/journal/micro/10.1099/mic.0.000220&mimeType=html&fmt=ahah

References

  1. Agnoli K., Lowe C. A., Farmer K. L., Husnain S. I., Thomas M. S. 2006; The ornibactin biosynthesis and transport genes of Burkholderia cenocepacia are regulated by an extracytoplasmic function sigma factor which is a part of the Fur regulon. J Bacteriol 188:3631–3644 [View Article][PubMed]
    [Google Scholar]
  2. Almeida R. S., Brunke S., Albrecht A., Thewes S., Laue M., Edwards J. E., Filler S. G., Hube B. 2008; The hyphal-associated adhesin and invasin Als3 of Candida albicans mediates iron acquisition from host ferritin. PLoS Pathog 4:e1000217 [View Article][PubMed]
    [Google Scholar]
  3. Almeida R. S., Wilson D., Hube B. 2009; Candida albicans iron acquisition within the host. FEMS Yeast Res 9:1000–1012 [View Article][PubMed]
    [Google Scholar]
  4. Ammendolia M. G., Bertuccini L., Iosi F., Minelli F., Berlutti F., Valenti P., Superti F. 2010; Bovine lactoferrin interacts with cable pili of Burkholderia cenocepacia . Biometals 23:531–542 [View Article][PubMed]
    [Google Scholar]
  5. Andersen S. B., Marvig R. L., Molin S., Krogh Johansen H., Griffin A. S. 2015; Long-term social dynamics drive loss of function in pathogenic bacteria. Proc Natl Acad Sci U S A 112:10756–10761 [View Article][PubMed]
    [Google Scholar]
  6. Asghar A. H., Shastri S., Dave E., Wowk I., Agnoli K., Cook A. M., Thomas M. S. 2011; The pobA gene of Burkholderia cenocepacia encodes a group I Sfp-type phosphopantetheinyltransferase required for biosynthesis of the siderophores ornibactin and pyochelin. Microbiology 157:349–361 [View Article][PubMed]
    [Google Scholar]
  7. Bakkal S., Robinson S. M., Ordonez C. L., Waltz D. A., Riley M. A. 2010; Role of bacteriocins in mediating interactions of bacterial isolates taken from cystic fibrosis patients. Microbiology 156:2058–2067 [View Article][PubMed]
    [Google Scholar]
  8. Banin E., Vasil M. L., Greenberg E. P. 2005; Iron and Pseudomonas aeruginosa biofilm formation. Proc Natl Acad Sci U S A 102:11076–11081 [View Article][PubMed]
    [Google Scholar]
  9. Beasley F. C., Vinés E. D., Grigg J. C., Zheng Q., Liu S., Lajoie G. A., Murphy M. E., Heinrichs D. E. 2009; Characterization of staphyloferrin A biosynthetic and transport mutants in Staphylococcus aureus . Mol Microbiol 72:947–963 [View Article][PubMed]
    [Google Scholar]
  10. Beasley F. C., Marolda C. L., Cheung J., Buac S., Heinrichs D. E. 2011; Staphylococcus aureus transporters Hts, Sir, and Sst capture iron liberated from human transferrin by staphyloferrin A, staphyloferrin B, and catecholamine stress hormones, respectively, and contribute to virulence. Infect Immun 79:2345–2355 [View Article][PubMed]
    [Google Scholar]
  11. Beaumont C., Delaby C. 2009; Recycling iron in normal and pathological states. Semin Hematol 46:328–338 [View Article][PubMed]
    [Google Scholar]
  12. Berlutti F., Morea C., Battistoni A., Sarli S., Cipriani P., Superti F., Ammendolia M. G., Valenti P. 2005; Iron availability influences aggregation, biofilm, adhesion and invasion of Pseudomonas aeruginosa and Burkholderia cenocepacia . Int J Immunopathol Pharmacol 18:661–670
    [Google Scholar]
  13. Berlutti F., Superti F., Nicoletti M., Morea C., Frioni A., Ammendolia M. G., Battistoni A., Valenti P. 2008; Bovine lactoferrin inhibits the efficiency of invasion of respiratory A549 cells of different iron-regulated morphological forms of Pseudomonas aeruginosa and Burkholderia cenocepacia . Int J Immunopathol Pharmacol 21:51–59
    [Google Scholar]
  14. Blatzer M., Binder U., Haas H. 2011; The metalloreductase FreB is involved in adaptation of Aspergillus fumigatus to iron starvation. Fungal Genet Biol 48:1027–1033 [View Article][PubMed]
    [Google Scholar]
  15. Boucher R. C. 2007; Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Annu Rev Med 58:157–170 [View Article][PubMed]
    [Google Scholar]
  16. Braun V., Pramanik A., Gwinner T., Köberle M., Bohn E. 2009; Sideromycins: tools and antibiotics. Biometals 22:3–13 [View Article][PubMed]
    [Google Scholar]
  17. Briard B., Bomme P., Lechner B. E., Mislin G. L., Lair V., Prévost M. C., Latgé J. P., Haas H., Beauvais A. 2015; Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines. Sci Rep 5:8220 [View Article][PubMed]
    [Google Scholar]
  18. Brickman T. J., Armstrong S. K. 2012; Iron and pH-responsive FtrABCD ferrous iron utilization system of Bordetella species. Mol Microbiol 86:580–593 [View Article][PubMed]
    [Google Scholar]
  19. Briskot G., Taraz K., Budzikiewicz H. 1986; [Pyoverdin-type siderophores from Pseudomonas aeruginosa]. Z Naturforsch C 41:497–506 (in German)
    [Google Scholar]
  20. Britigan B. E., Hayek M. B., Doebbeling B. N., Fick R. B. Jr 1993; Transferrin and lactoferrin undergo proteolytic cleavage in the Pseudomonas aeruginosa-infected lungs of patients with cystic fibrosis. Infect Immun 61:5049–5055
    [Google Scholar]
  21. Bullen J. J. 1981; The significance of iron in infection. Rev Infect Dis 3:1127–1138 [View Article][PubMed]
    [Google Scholar]
  22. Burgel P. R., Bellis G., Olesen H. V., Viviani L., Zolin A., Blasi F., Elborn J. 2015; Future trends in cystic fibrosis demography in 34 European countries. Eur Respir J 46:133–141 [View Article][PubMed]
    [Google Scholar]
  23. Calcott M. J., Ackerley D. F. 2014; Genetic manipulation of non-ribosomal peptide synthetases to generate novel bioactive peptide products. Biotechnol Lett 36:2407–2416 [View Article][PubMed]
    [Google Scholar]
  24. Calcott M. J., Owen J. G., Lamont I. L., Ackerley D. F. 2014; Biosynthesis of novel pyoverdines by domain substitution in a nonribosomal peptide synthetase of Pseudomonas aeruginosa . Appl Environ Microbiol 80:5723–5731 [View Article][PubMed]
    [Google Scholar]
  25. Carmody L. A., Zhao J., Kalikin L. M., LeBar W., Simon R. H., Venkataraman A., Schmidt T. M., Abdo Z., Schloss P. D., LiPuma J. J. 2015; The daily dynamics of cystic fibrosis airway microbiota during clinical stability and at exacerbation. Microbiome 3:12 [View Article][PubMed]
    [Google Scholar]
  26. Cartron M. L., Maddocks S., Gillingham P., Craven C. J., Andrews S. C. 2006; Feo - transport of ferrous iron into bacteria. Biometals 19:143–157 [View Article][PubMed]
    [Google Scholar]
  27. Caverly L. J., Zhao J., LiPuma J. J. 2015; Cystic fibrosis lung microbiome: opportunities to reconsider management of airway infection. Pediatr Pulmonol 50:(Suppl 40)S31–S38 [View Article][PubMed]
    [Google Scholar]
  28. Caza M., Kronstad J. W. 2013; Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans. Front Cell Infect Microbiol 3:80
    [Google Scholar]
  29. Cézard C., Farvacques N., Sonnet P. 2015; Chemistry and biology of pyoverdines, Pseudomonas primary siderophores. Curr Med Chem 22:165–186 [View Article][PubMed]
    [Google Scholar]
  30. Chen A. I., Dolben E. F., Okegbe C., Harty C. E., Golub Y., Thao S., Ha D. G., Willger S. D., O'Toole G. A., other authors. 2014; Candida albicans ethanol stimulates Pseudomonas aeruginosa WspR-controlled biofilm formation as part of a cyclic relationship involving phenazines. PLoS Pathog 10:e1004480 [View Article][PubMed]
    [Google Scholar]
  31. Cheung J., Beasley F. C., Liu S., Lajoie G. A., Heinrichs D. E. 2009; Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus . Mol Microbiol 74:594–608 [View Article][PubMed]
    [Google Scholar]
  32. Chotirmall S. H., Greene C. M., McElvaney N. G. 2010; Candida species in cystic fibrosis: a road less travelled. Med Mycol 48:(Suppl 1)S114–S124 [View Article][PubMed]
    [Google Scholar]
  33. Coburn B., Wang P. W., Diaz Caballero J., Clark S. T., Brahma V., Donaldson S., Zhang Y., Surendra A., Gong Y., other authors. 2015; Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep 5:10241 [View Article][PubMed]
    [Google Scholar]
  34. Cornelis P. 2010; Iron uptake and metabolism in pseudomonads. Appl Microbiol Biotechnol 86:1637–1645 [View Article][PubMed]
    [Google Scholar]
  35. Cornelis P., Bodilis J. 2009; A survey of TonB-dependent receptors in fluorescent pseudomonads. Environ Microbiol Rep 1:256–262 [View Article][PubMed]
    [Google Scholar]
  36. Cornelis P., Dingemans J. 2013; Pseudomonas aeruginosa adapts its iron uptake strategies in function of the type of infections. Front Cell Infect Microbiol 3:75
    [Google Scholar]
  37. Cox C. D., Adams P. 1985; Siderophore activity of pyoverdin for Pseudomonas aeruginosa . Infect Immun 48:130–138
    [Google Scholar]
  38. Cox C. D., Graham R. 1979; Isolation of an iron-binding compound from Pseudomonas aeruginosa . J Bacteriol 137:357–364
    [Google Scholar]
  39. Cuív P. O., Clarke P., O'Connell M. 2006; Identification and characterization of an iron-regulated gene, chtA, required for the utilization of the xenosiderophores aerobactin, rhizobactin 1021 and schizokinen by Pseudomonas aeruginosa . Microbiology 152:945–954 [View Article][PubMed]
    [Google Scholar]
  40. Cuív P. O., 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 [View Article][PubMed]
    [Google Scholar]
  41. Darling P., Chan M., Cox A. D., Sokol P. A. 1998; Siderophore production by cystic fibrosis isolates of Burkholderia cepacia . Infect Immun 66:874–877
    [Google Scholar]
  42. de Carvalho C. C., Fernandes P. 2014; Siderophores as Trojan Horses: tackling multidrug resistance?. Front Microbiol 5:290 [View Article][PubMed]
    [Google Scholar]
  43. De Vos D., De Chial M., Cochez C., Jansen S., Tümmler B., Meyer J. M., Cornelis P. 2001; Study of pyoverdine type and production by Pseudomonas aeruginosa isolated from cystic fibrosis patients: prevalence of type II pyoverdine isolates and accumulation of pyoverdine-negative mutations. Arch Microbiol 175:384–388 [View Article][PubMed]
    [Google Scholar]
  44. Dehner C., Morales-Soto N., Behera R. K., Shrout J., Theil E. C., Maurice P. A., Dubois J. L. 2013; Ferritin and ferrihydrite nanoparticles as iron sources for Pseudomonas aeruginosa . J Biol Inorg Chem 18:371–381 [View Article][PubMed]
    [Google Scholar]
  45. Delfani S., Mohabati Mobarez A., Imani Fooladi A. A., Amani J., Emaneini M. 2015; Protection of mice against Staphylococcus aureus infection by a recombinant protein ClfA-IsdB-Hlg as a vaccine candidate. Med Microbiol Immunol (Berl) [View Article][PubMed]
    [Google Scholar]
  46. Denayer S., Matthijs S., Cornelis P. 2007; Pyocin S2 (Sa) kills Pseudomonas aeruginosa strains via the FpvA type I ferripyoverdine receptor. J Bacteriol 189:7663–7668 [View Article][PubMed]
    [Google Scholar]
  47. Denman C. C., Robinson M. T., Sass A. M., Mahenthiralingam E., Brown A. R. 2014; Growth on mannitol-rich media elicits a genome-wide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner. Microbiology 160:187–197 [View Article][PubMed]
    [Google Scholar]
  48. Donovan A., Lima C. A., Pinkus J. L., Pinkus G. S., Zon L. I., Robine S., Andrews N. C. 2005; The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab 1:191–200 [View Article][PubMed]
    [Google Scholar]
  49. Dumas Z., Ross-Gillespie A., Kümmerli R. 2013; Switching between apparently redundant iron-uptake mechanisms benefits bacteria in changeable environments. Proc Biol Sci 280:20131055 [View Article][PubMed]
    [Google Scholar]
  50. Eisendle M., Oberegger H., Zadra I., Haas H. 2003; The siderophore system is essential for viability of Aspergillus nidulans: functional analysis of two genes encoding l-ornithine N 5-monooxygenase (sidA) and a non-ribosomal peptide synthetase (sidC). Mol Microbiol 49:359–375 [View Article][PubMed]
    [Google Scholar]
  51. Elfarash A., Dingemans J., Ye L., Hassan A. A., Craggs M., Reimmann C., Thomas M. S., Cornelis P. 2014; Pore-forming pyocin S5 utilizes the FptA ferripyochelin receptor to kill Pseudomonas aeruginosa . Microbiology 160:261–269 [View Article][PubMed]
    [Google Scholar]
  52. Elias S., Degtyar E., Banin E. 2011; FvbA is required for vibriobactin utilization in Pseudomonas aeruginosa . Microbiology 157:2172–2180 [View Article][PubMed]
    [Google Scholar]
  53. Fardeau S., Dassonville-Klimpt A., Audic N., Sasaki A., Pillon M., Baudrin E., Mullié C., Sonnet P. 2014; Synthesis and antibacterial activity of catecholate-ciprofloxacin conjugates. Bioorg Med Chem 22:4049–4060 [View Article][PubMed]
    [Google Scholar]
  54. Ferreira J. A., Penner J. C., Moss R. B., Haagensen J. A., Clemons K. V., Spormann A. M., Nazik H., Cohen K., Banaei N., other authors. 2015; Inhibition of Aspergillus fumigatus and its biofilm by Pseudomonas aeruginosa is dependent on the source, phenotype and growth conditions of the bacterium. PLoS One 10:e0134692 [View Article][PubMed]
    [Google Scholar]
  55. Filkins L. M., Graber J. A., Olson D. G., Dolben E. L., Lynd L. R., Bhuju S., O'Toole G. A. 2015; Coculture of Staphylococcus aureus with Pseudomonas aeruginosa drives S. aureus towards fermentative metabolism and reduced viability in a cystic fibrosis model. J Bacteriol 197:2252–2264 [View Article][PubMed]
    [Google Scholar]
  56. Flight W. G., Smith A., Paisey C., Marchesi J. R., Bull M. J., Norville P. J., Mutton K. J., Webb A. K., Bright-Thomas R. J., other authors. 2015; Rapid detection of emerging pathogens and loss of microbial diversity associated with severe lung disease in cystic fibrosis. J Clin Microbiol 53:2022–2029 [View Article][PubMed]
    [Google Scholar]
  57. Fluckinger M., Haas H., Merschak P., Glasgow B. J., Redl B. 2004; Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores. Antimicrob Agents Chemother 48:3367–3372 [View Article][PubMed]
    [Google Scholar]
  58. Fowler V. G., Allen K. B., Moreira E. D., Moustafa M., Isgro F., Boucher H. W., Corey G. R., Carmeli Y., Betts R., other authors. 2013; Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA 309:1368–1378 [View Article][PubMed]
    [Google Scholar]
  59. Freestone P. P., Sandrini S. M., Haigh R. D., Lyte M. 2008; Microbial endocrinology: how stress influences susceptibility to infection. Trends Microbiol 16:55–64 [View Article][PubMed]
    [Google Scholar]
  60. Friedman D. B., Stauff D. L., Pishchany G., Whitwell C. W., Torres V. J., Skaar E. P. 2006; Staphylococcus aureus redirects central metabolism to increase iron availability. PLoS Pathog 2:e87 [View Article][PubMed]
    [Google Scholar]
  61. Ganz T., Nemeth E. 2015; Iron homeostasis in host defence and inflammation. Nat Rev Immunol 15:500–510 [View Article][PubMed]
    [Google Scholar]
  62. García C. A., Passerini De Rossi B., Alcaraz E., Vay C., Franco M. 2012; Siderophores of Stenotrophomonas maltophilia: detection and determination of their chemical nature. Rev Argent Microbiol 44:150–154
    [Google Scholar]
  63. Ghio A. J., Roggli V. L., Soukup J. M., Richards J. H., Randell S. H., Muhlebach M. S. 2013; Iron accumulates in the lavage and explanted lungs of cystic fibrosis patients. J Cyst Fibros 12:390–398 [View Article][PubMed]
    [Google Scholar]
  64. Gifford A. H., Moulton L. A., Dorman D. B., Olbina G., Westerman M., Parker H. W., Stanton B. A., O'Toole G. A. 2012; Iron homeostasis during cystic fibrosis pulmonary exacerbation. Clin Transl Sci 5:368–373 [View Article][PubMed]
    [Google Scholar]
  65. Gileles-Hillel A., Shoseyov D., Polacheck I., Korem M., Kerem E., Cohen-Cymberknoh M. 2015; Association of chronic Candida albicans respiratory infection with a more severe lung disease in patients with cystic fibrosis. Pediatr Pulmonol 50:1082–1089 [View Article][PubMed]
    [Google Scholar]
  66. Goetz D. H., Holmes M. A., Borregaard N., Bluhm M. E., Raymond K. N., Strong R. K. 2002; The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 10:1033–1043 [View Article][PubMed]
    [Google Scholar]
  67. Górska A., Sloderbach A., Marszałł M. P. 2014; Siderophore-drug complexes: potential medicinal applications of the ‘Trojan horse’ strategy. Trends Pharmacol Sci 35:442–449 [View Article][PubMed]
    [Google Scholar]
  68. Gray R. D., Duncan A., Noble D., Imrie M., O'Reilly D. S., Innes J. A., Porteous D. J., Greening A. P., Boyd A. C. 2010; Sputum trace metals are biomarkers of inflammatory and suppurative lung disease. Chest 137:635–641 [View Article][PubMed]
    [Google Scholar]
  69. Grigg J. C., Vermeiren C. L., Heinrichs D. E., Murphy M. E. 2007; Heme coordination by Staphylococcus aureus IsdE. J Biol Chem 282:28815–28822 [View Article][PubMed]
    [Google Scholar]
  70. Grigg J. C., Ukpabi G., Gaudin C. F., Murphy M. E. 2010; Structural biology of heme binding in the Staphylococcus aureus Isd system. J Inorg Biochem 104:341–348 [View Article][PubMed]
    [Google Scholar]
  71. Haas H. 2003; Molecular genetics of fungal siderophore biosynthesis and uptake: the role of siderophores in iron uptake and storage. Appl Microbiol Biotechnol 62:316–330 [View Article][PubMed]
    [Google Scholar]
  72. Haas H. 2012; Iron - a key nexus in the virulence of Aspergillus fumigatus . Front Microbiol 3:28 [View Article][PubMed]
    [Google Scholar]
  73. Haley K. P., Skaar E. P. 2012; A battle for iron: host sequestration and Staphylococcus aureus acquisition. Microbes Infect 14:217–227 [View Article][PubMed]
    [Google Scholar]
  74. Hammer N. D., Skaar E. P. 2011; Molecular mechanisms of Staphylococcus aureus iron acquisition. Annu Rev Microbiol 65:129–147 [View Article][PubMed]
    [Google Scholar]
  75. Hannauer M., Barda Y., Mislin G. L., Shanzer A., Schalk I. J. 2010; The ferrichrome uptake pathway in Pseudomonas aeruginosa involves an iron release mechanism with acylation of the siderophore and recycling of the modified desferrichrome. J Bacteriol 192:1212–1220 [View Article][PubMed]
    [Google Scholar]
  76. Hannauer M., Arifin A. J., Heinrichs D. E. 2015; Involvement of reductases IruO and NtrA in iron acquisition by Staphylococcus aureus . Mol Microbiol 96:1192–1210 [View Article][PubMed]
    [Google Scholar]
  77. Harrison F., Paul J., Massey R. C., Buckling A. 2008; Interspecific competition and siderophore-mediated cooperation in Pseudomonas aeruginosa . ISME J 2:49–55 [View Article][PubMed]
    [Google Scholar]
  78. Heinrichs D. E., Young L., Poole K. 1991; Pyochelin-mediated iron transport in Pseudomonas aeruginosa: involvement of a high-molecular-mass outer membrane protein. Infect Immun 59:3680–3684
    [Google Scholar]
  79. Heymann P., Gerads M., Schaller M., Dromer F., Winkelmann G., Ernst J. F. 2002; The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion. Infect Immun 70:5246–5255 [View Article][PubMed]
    [Google Scholar]
  80. Hissen A. H., Moore M. M. 2005; Site-specific rate constants for iron acquisition from transferrin by the Aspergillus fumigatus siderophores N′,N″,N‴-triacetylfusarinine C and ferricrocin. J Biol Inorg Chem 10:211–220 [View Article][PubMed]
    [Google Scholar]
  81. Hissen A. H., Chow J. M., 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 [View Article][PubMed]
    [Google Scholar]
  82. Hissen A. H., Wan A. N., Warwas M. L., Pinto L. J., Moore M. M. 2005; The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding l-ornithine N 5-oxygenase, is required for virulence. Infect Immun 73:5493–5503 [View Article][PubMed]
    [Google Scholar]
  83. Hofer B., Dantier C., Gebhardt K., Desarbre E., Schmitt-Hoffmann A., Page M. G. 2013; Combined effects of the siderophore monosulfactam BAL30072 and carbapenems on multidrug-resistant Gram-negative bacilli. J Antimicrob Chemother 68:1120–1129 [View Article][PubMed]
    [Google Scholar]
  84. Holzberg M., Artis W. M. 1983; Hydroxamate siderophore production by opportunistic and systemic fungal pathogens. Infect Immun 40:1134–1139
    [Google Scholar]
  85. Hom K., Heinzl G. A., Eakanunkul S., Lopes P. E., Xue F., MacKerell A. D. Jr, Wilks A. 2013; Small molecule antivirulents targeting the iron-regulated heme oxygenase (HemO) of P. aeruginosa . J Med Chem 56:2097–2109 [View Article][PubMed]
    [Google Scholar]
  86. Hunter R. C., Asfour F., Dingemans J., Osuna B. L., Samad T., Malfroot A., Cornelis P., Newman D. K. 2013; Ferrous iron is a significant component of bioavailable iron in cystic fibrosis airways. MBio 4:e00557-13 [View Article][PubMed]
    [Google Scholar]
  87. Ibrahim A. S., Gebremariam T., French S. W., Edwards J. E. Jr, Spellberg B. 2010; The iron chelator deferasirox enhances liposomal amphotericin B efficacy in treating murine invasive pulmonary aspergillosis. J Antimicrob Chemother 65:289–292 [View Article][PubMed]
    [Google Scholar]
  88. Ibrahim A. S., Gebremariam T., Luo G., Fu Y., French S. W., Edwards J. E. Jr, Spellberg B. 2011; Combination therapy of murine mucormycosis or aspergillosis with iron chelation, polyenes, and echinocandins. Antimicrob Agents Chemother 55:1768–1770 [View Article][PubMed]
    [Google Scholar]
  89. Imperi F., Massai F., Facchini M., Frangipani E., Visaggio D., Leoni L., Bragonzi A., Visca P. 2013; Repurposing the antimycotic drug flucytosine for suppression of Pseudomonas aeruginosa pathogenicity. Proc Natl Acad Sci U S A 110:7458–7463 [View Article][PubMed]
    [Google Scholar]
  90. Ismail A., Bedell G. W., Lupan D. M. 1985; Siderophore production by the pathogenic yeast, Candida albicans . Biochem Biophys Res Commun 130:885–891 [View Article][PubMed]
    [Google Scholar]
  91. Kaur A. P., Lansky I. B., Wilks A. 2009; The role of the cytoplasmic heme-binding protein (PhuS) of Pseudomonas aeruginosa in intracellular heme trafficking and iron homeostasis. J Biol Chem 284:56–66 [View Article][PubMed]
    [Google Scholar]
  92. Kerr J. R., Taylor G. W., Rutman A., Høiby N., Cole P. J., Wilson R. 1999; Pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine inhibit fungal growth. J Clin Pathol 52:385–387 [View Article][PubMed]
    [Google Scholar]
  93. Kim S. J., Park R. Y., Kang S. M., Choi M. H., Kim C. M., Shin S. H. 2006; Pseudomonas aeruginosa alkaline protease can facilitate siderophore-mediated iron-uptake via the proteolytic cleavage of transferrins. Biol Pharm Bull 29:2295–2300 [View Article][PubMed]
    [Google Scholar]
  94. Knight S. A., Lesuisse E., Stearman R., Klausner R. D., Dancis A. 2002; Reductive iron uptake by Candida albicans: role of copper, iron and the TUP1 regulator. Microbiology 148:29–40 [View Article][PubMed]
    [Google Scholar]
  95. Konings A. F., Martin L. W., Sharples K. J., Roddam L. F., Latham R., Reid D. W., Lamont I. L. 2013; Pseudomonas aeruginosa uses multiple pathways to acquire iron during chronic infection in cystic fibrosis lungs. Infect Immun 81:2697–2704 [View Article][PubMed]
    [Google Scholar]
  96. Kuznets G., Vigonsky E., Weissman Z., Lalli D., Gildor T., Kauffman S. J., Turano P., Becker J., Lewinson O., Kornitzer D. 2014; A relay network of extracellular heme-binding proteins drives C. albicans iron acquisition from hemoglobin. PLoS Pathog 10:e1004407 [View Article][PubMed]
    [Google Scholar]
  97. Lamb A. L. 2015; Breaking a pathogen's iron will: inhibiting siderophore production as an antimicrobial strategy. Biochim Biophys Acta 1854:1054–1070 [View Article][PubMed]
    [Google Scholar]
  98. Lamont I. L., Konings A. F., Reid D. W. 2009; Iron acquisition by Pseudomonas aeruginosa in the lungs of patients with cystic fibrosis. Biometals 22:53–60 [View Article][PubMed]
    [Google Scholar]
  99. Landman D., Singh M., El-Imad B., Miller E., Win T., Quale J. 2014; In vitro activity of the siderophore monosulfactam BAL30072 against contemporary Gram-negative pathogens from New York City, including multidrug-resistant isolates. Int J Antimicrob Agents 43:527–532 [View Article][PubMed]
    [Google Scholar]
  100. Ledala N., Zhang B., Seravalli J., Powers R., Somerville G. A. 2014; Influence of iron and aeration on Staphylococcus aureus growth, metabolism, and transcription. J Bacteriol 196:2178–2189 [View Article][PubMed]
    [Google Scholar]
  101. Lin M. H., Shu J. C., Huang H. Y., Cheng Y. C. 2012; Involvement of iron in biofilm formation by Staphylococcus aureus . PLoS One 7:e34388 [View Article][PubMed]
    [Google Scholar]
  102. LiPuma J. J. 2010; The changing microbial epidemiology in cystic fibrosis. Clin Microbiol Rev 23:299–323 [View Article][PubMed]
    [Google Scholar]
  103. Liu P. V., Shokrani F. 1978; Biological activities of pyochelins: iron-chelating agents of Pseudomonas aeruginosa . Infect Immun 22:878–890
    [Google Scholar]
  104. Llamas M. A., Sparrius M., Kloet R., Jiménez C. R., Vandenbroucke-Grauls C., Bitter W. 2006; The heterologous siderophores ferrioxamine B and ferrichrome activate signaling pathways in Pseudomonas aeruginosa . J Bacteriol 188:1882–1891 [View Article][PubMed]
    [Google Scholar]
  105. Llamas M. A., Mooij M. J., Sparrius M., Vandenbroucke-Grauls C. M., Ratledge C., Bitter W. 2008; Characterization of five novel Pseudomonas aeruginosa cell-surface signalling systems. Mol Microbiol 67:458–472 [View Article][PubMed]
    [Google Scholar]
  106. Lubamba B., Dhooghe B., Noel S., Leal T. 2012; Cystic fibrosis: insight into CFTR pathophysiology and pharmacotherapy. Clin Biochem 45:1132–1144 [View Article][PubMed]
    [Google Scholar]
  107. Mahenthiralingam E., Urban T. A., Goldberg J. B. 2005; The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol 3:144–156 [View Article][PubMed]
    [Google Scholar]
  108. Mariotti P., Malito E., Biancucci M., Lo Surdo P., Mishra R. P., Nardi-Dei V., Savino S., Nissum M., Spraggon G., other authors. 2013; Structural and functional characterization of the Staphylococcus aureus virulence factor and vaccine candidate FhuD2. Biochem J 449:683–693 [View Article][PubMed]
    [Google Scholar]
  109. Martin L. W., Reid D. W., Sharples K. J., Lamont I. L. 2011; Pseudomonas siderophores in the sputum of patients with cystic fibrosis. Biometals 24:1059–1067 [View Article][PubMed]
    [Google Scholar]
  110. Marvig R. L., Damkiær S., Khademi S. M., Markussen T. M., Molin S., Jelsbak L. 2014; Within-host evolution of Pseudomonas aeruginosa reveals adaptation toward iron acquisition from hemoglobin. MBio 5:e00966-14 [View Article][PubMed]
    [Google Scholar]
  111. Mashburn L. M., Jett A. M., Akins D. R., Whiteley M. 2005; Staphylococcus aureus serves as an iron source for Pseudomonas aeruginosa during in vivo coculture. J Bacteriol 187:554–566 [View Article][PubMed]
    [Google Scholar]
  112. Mathew A., Eberl L., Carlier A. L. 2014; A novel siderophore-independent strategy of iron uptake in the genus Burkholderia . Mol Microbiol 91:805–820 [View Article][PubMed]
    [Google Scholar]
  113. Mazmanian S. K., Ton-That H., Su K., Schneewind O. 2002; An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis. Proc Natl Acad Sci U S A 99:2293–2298 [View Article][PubMed]
    [Google Scholar]
  114. Mazmanian S. K., Skaar E. P., Gaspar A. H., Humayun M., Gornicki P., Jelenska J., Joachmiak A., Missiakas D. M., Schneewind O. 2003; Passage of heme-iron across the envelope of Staphylococcus aureus . Science 299:906–909 [View Article][PubMed]
    [Google Scholar]
  115. McKenney D., Brown K. E., Allison D. G. 1995; Influence of Pseudomonas aeruginosa exoproducts on virulence factor production in Burkholderia cepacia: evidence of interspecies communication. J Bacteriol 177:6989–6992
    [Google Scholar]
  116. Meyer J. M., Hohnadel D., Hallé F. 1989; Cepabactin from Pseudomonas cepacia, a new type of siderophore. J Gen Microbiol 135:1479–1487
    [Google Scholar]
  117. Meyer J. M., Van V. T., Stintzi A., Berge O., Winkelmann G. 1995; Ornibactin production and transport properties in strains of Burkholderia vietnamiensis and Burkholderia cepacia (formerly Pseudomonas cepacia). Biometals 8:309–317 [View Article][PubMed]
    [Google Scholar]
  118. Meyer J. M., Neely A., Stintzi A., Georges C., Holder I. A. 1996; Pyoverdin is essential for virulence of Pseudomonas aeruginosa . Infect Immun 64:518–523
    [Google Scholar]
  119. Michel L., González N., Jagdeep S., Nguyen-Ngoc T., Reimmann C. 2005; PchR-box recognition by the AraC-type regulator PchR of Pseudomonas aeruginosa requires the siderophore pyochelin as an effector. Mol Microbiol 58:495–509 [View Article][PubMed]
    [Google Scholar]
  120. Minnick A. A., McKee J. A., Dolence E. K., Miller M. J. 1992; Iron transport-mediated antibacterial activity of and development of resistance to hydroxamate and catechol siderophore-carbacephalosporin conjugates. Antimicrob Agents Chemother 36:840–850 [View Article][PubMed]
    [Google Scholar]
  121. Mishra R. P., Mariotti P., Fiaschi L., Nosari S., Maccari S., Liberatori S., Fontana M. R., Pezzicoli A., De Falco M. G., other authors. 2012; Staphylococcus aureus FhuD2 is involved in the early phase of staphylococcal dissemination and generates protective immunity in mice. J Infect Dis 206:1041–1049 [View Article][PubMed]
    [Google Scholar]
  122. Mislin G. L., Schalk I. J. 2014; Siderophore-dependent iron uptake systems as gates for antibiotic Trojan horse strategies against Pseudomonas aeruginosa . Metallomics 6:408–420 [View Article][PubMed]
    [Google Scholar]
  123. Möllmann U., Heinisch L., Bauernfeind A., Köhler T., Ankel-Fuchs D. 2009; Siderophores as drug delivery agents: application of the Trojan Horse strategy. Biometals 22:615–624 [View Article][PubMed]
    [Google Scholar]
  124. Moon C. D., Zhang X. X., Matthijs S., Schäfer M., Budzikiewicz H., Rainey P. B. 2008; Genomic, genetic and structural analysis of pyoverdine-mediated iron acquisition in the plant growth-promoting bacterium Pseudomonas fluorescens SBW25. BMC Microbiol 87 [View Article][PubMed]
    [Google Scholar]
  125. Moore M. M. 2013; The crucial role of iron uptake in Aspergillus fumigatus virulence. Curr Opin Microbiol 16:692–699 [View Article][PubMed]
    [Google Scholar]
  126. Morales D. K., Grahl N., Okegbe C., Dietrich L. E., Jacobs N. J., Hogan D. A. 2013; Control of Candida albicans metabolism and biofilm formation by Pseudomonas aeruginosa phenazines. MBio 4:e00526-12 [View Article][PubMed]
    [Google Scholar]
  127. Moreau-Marquis S., Bomberger J. M., Anderson G. G., Swiatecka-Urban A., Ye S., O'Toole G. A., Stanton B. A. 2008; The DeltaF508-CFTR mutation results in increased biofilm formation by Pseudomonas aeruginosa by increasing iron availability. Am J Physiol Lung Cell Mol Physiol 295:L25–L37 [View Article][PubMed]
    [Google Scholar]
  128. Moreau-Marquis S., O'Toole G. A., Stanton B. A. 2009; Tobramycin and FDA-approved iron chelators eliminate Pseudomonas aeruginosa biofilms on cystic fibrosis cells. Am J Respir Cell Mol Biol 41:305–313 [View Article][PubMed]
    [Google Scholar]
  129. Moreau-Marquis S., Coutermarsh B., Stanton B. A. 2015; Combination of hypothiocyanite and lactoferrin (ALX-109) enhances the ability of tobramycin and aztreonam to eliminate Pseudomonas aeruginosa biofilms growing on cystic fibrosis airway epithelial cells. J Antimicrob Chemother 70:160–166 [View Article][PubMed]
    [Google Scholar]
  130. Moree W. J., Phelan V. V., Wu C. H., Bandeira N., Cornett D. S., Duggan B. M., Dorrestein P. C. 2012; Interkingdom metabolic transformations captured by microbial imaging mass spectrometry. Proc Natl Acad Sci U S A 109:13811–13816 [View Article][PubMed]
    [Google Scholar]
  131. Morton D. J., Madore L. L., Smith A., Vanwagoner T. M., Seale T. W., Whitby P. W., Stull T. L. 2005; The heme-binding lipoprotein (HbpA) of Haemophilus influenzae: role in heme utilization. FEMS Microbiol Lett 253:193–199 [View Article][PubMed]
    [Google Scholar]
  132. Morton D. J., Seale T. W., Bakaletz L. O., Jurcisek J. A., Smith A., VanWagoner T. M., Whitby P. W., Stull T. L. 2009; The heme-binding protein (HbpA) of Haemophilus influenzae as a virulence determinant. Int J Med Microbiol 299:479–488 [View Article][PubMed]
    [Google Scholar]
  133. Morton D. J., Turman E. J., Hensley P. D., VanWagoner T. M., Seale T. W., Whitby P. W., Stull T. L. 2010; Identification of a siderophore utilization locus in nontypeable Haemophilus influenzae . BMC Microbiol 10:113 [View Article][PubMed]
    [Google Scholar]
  134. Nemeth E., Rivera S., Gabayan V., Keller C., Taudorf S., Pedersen B. K., Ganz T. 2004a; IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113:1271–1276 [View Article][PubMed]
    [Google Scholar]
  135. Nemeth E., Tuttle M. S., Powelson J., Vaughn M. B., Donovan A., Ward D. M., Ganz T., Kaplan J. 2004b; Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093 [View Article][PubMed]
    [Google Scholar]
  136. Nguyen A. T., Oglesby-Sherrouse A. G. 2015; Spoils of war: iron at the crux of clinical and ecological fitness of Pseudomonas aeruginosa . Biometals 28:433–443 [View Article][PubMed]
    [Google Scholar]
  137. Nguyen A. T., O'Neill M. J., Watts A. M., Robson C. L., Lamont I. L., Wilks A., Oglesby-Sherrouse A. G. 2014; Adaptation of iron homeostasis pathways by a Pseudomonas aeruginosa pyoverdine mutant in the cystic fibrosis lung. J Bacteriol 196:2265–2276 [View Article][PubMed]
    [Google Scholar]
  138. Noni M., Katelari A., Dimopoulos G., Doudounakis S. E., Tzoumaka-Bakoula C., Spoulou V. 2015; Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship. Eur J Clin Microbiol Infect Dis 34:2235–2241 [View Article][PubMed]
    [Google Scholar]
  139. Ochsner U. A., Johnson Z., Vasil M. L. 2000; Genetics and regulation of two distinct haem-uptake systems, phu and has, in Pseudomonas aeruginosa . Microbiology 146:185–198 [View Article][PubMed]
    [Google Scholar]
  140. Ochsner U. A., Wilderman P. J., Vasil A. I., Vasil M. L. 2002; GeneChip expression analysis of the iron starvation response in Pseudomonas aeruginosa: identification of novel pyoverdine biosynthesis genes. Mol Microbiol 45:1277–1287 [View Article][PubMed]
    [Google Scholar]
  141. Okamoto-Shibayama K., Kikuchi Y., Kokubu E., Sato Y., Ishihara K. 2014; Csa2, a member of the Rbt5 protein family, is involved in the utilization of iron from human hemoglobin during Candida albicans hyphal growth. FEMS Yeast Res 14:674–677 [View Article][PubMed]
    [Google Scholar]
  142. Oosthuizen J. L., Gomez P., Ruan J., Hackett T. L., Moore M. M., Knight D. A., Tebbutt S. J. 2011; Dual organism transcriptomics of airway epithelial cells interacting with conidia of Aspergillus fumigatus . PLoS One 6:e20527 [View Article][PubMed]
    [Google Scholar]
  143. Paganin P., Fiscarelli E. V., Tuccio V., Chiancianesi M., Bacci G., Morelli P., Dolce D., Dalmastri C., De Alessandri A., other authors. 2015; Changes in cystic fibrosis airway microbial community associated with a severe decline in lung function. PLoS One 10:e0124348 [View Article][PubMed]
    [Google Scholar]
  144. Page M. G., Dantier C., Desarbre E. 2010; In vitro properties of BAL30072, a novel siderophore sulfactam with activity against multiresistant Gram-negative bacilli. Antimicrob Agents Chemother 54:2291–2302 [View Article][PubMed]
    [Google Scholar]
  145. Panek H., O'Brian M. R. 2002; A whole genome view of prokaryotic haem biosynthesis. Microbiology 148:2273–2282 [View Article][PubMed]
    [Google Scholar]
  146. Parkins M. D., Floto R. A. 2015; Emerging bacterial pathogens and changing concepts of bacterial pathogenesis in cystic fibrosis. J Cyst Fibros 14:293–304 [View Article][PubMed]
    [Google Scholar]
  147. Parrow N. L., Fleming R. E., Minnick M. F. 2013; Sequestration and scavenging of iron in infection. Infect Immun 81:3503–3514 [View Article][PubMed]
    [Google Scholar]
  148. Petrik M., Franssen G. M., Haas H., Laverman P., Hörtnagl C., Schrettl M., Helbok A., Lass-Flörl C., Decristoforo C. 2012; Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging. Eur J Nucl Med Mol Imaging 39:1175–1183 [View Article][PubMed]
    [Google Scholar]
  149. Pond M. N., Morton A. M., Conway S. P. 1996; Functional iron deficiency in adults with cystic fibrosis. Respir Med 90:409–413 [View Article][PubMed]
    [Google Scholar]
  150. Ramanan N., Wang Y. 2000; A high-affinity iron permease essential for Candida albicans virulence. Science 288:1062–1064 [View Article][PubMed]
    [Google Scholar]
  151. Ravel J., Cornelis P. 2003; Genomics of pyoverdine-mediated iron uptake in pseudomonads. Trends Microbiol 11:195–200 [View Article][PubMed]
    [Google Scholar]
  152. Reid D. W., Withers N. J., Francis L., Wilson J. W., Kotsimbos T. C. 2002; Iron deficiency in cystic fibrosis: relationship to lung disease severity and chronic Pseudomonas aeruginosa infection. Chest 121:48–54 [View Article][PubMed]
    [Google Scholar]
  153. Reid D. W., Lam Q. T., Schneider H., Walters E. H. 2004; Airway iron and iron-regulatory cytokines in cystic fibrosis. Eur Respir J 24:286–291 [View Article][PubMed]
    [Google Scholar]
  154. Reid D. W., Carroll V., O'May C., Champion A., Kirov S. M. 2007; Increased airway iron as a potential factor in the persistence of Pseudomonas aeruginosa infection in cystic fibrosis. Eur Respir J 30:286–292 [View Article][PubMed]
    [Google Scholar]
  155. 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 [View Article][PubMed]
    [Google Scholar]
  156. Sabino R., Ferreira J. A., Moss R. B., Valente J., Veríssimo C., Carolino E., Clemons K. V., Everson C., Banaei N., other authors. 2015; Molecular epidemiology of Aspergillus collected from cystic fibrosis patients. J Cyst Fibros 14:474–481 [View Article][PubMed]
    [Google Scholar]
  157. Salsgiver E. L., Fink A. K., Knapp E. A., LiPuma J. J., Olivier K. N., Marshall B. C., Saiman L. 2015; Changing epidemiology of the respiratory bacteriology of patients with cystic fibrosis. Chest [View Article][PubMed]
    [Google Scholar]
  158. Sandrini S. M., Shergill R., Woodward J., Muralikuttan R., Haigh R. D., Lyte M., Freestone P. P. 2010; Elucidation of the mechanism by which catecholamine stress hormones liberate iron from the innate immune defense proteins transferrin and lactoferrin. J Bacteriol 192:587–594 [View Article][PubMed]
    [Google Scholar]
  159. Schrettl M., Bignell E., Kragl C., Joechl C., Rogers T., Arst H. N. Jr, Haynes K., Haas H. 2004; Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence. J Exp Med 200:1213–1219 [View Article][PubMed]
    [Google Scholar]
  160. Schrettl M., Bignell E., Kragl C., Sabiha Y., Loss O., Eisendle M., Wallner A., Arst H. N. Jr, Haynes K., Haas H. 2007; Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. PLoS Pathog 3:1195–1207 [View Article][PubMed]
    [Google Scholar]
  161. Schrettl M., Ibrahim-Granet O., Droin S., Huerre M., Latgé J. P., Haas H. 2010; The crucial role of the Aspergillus fumigatus siderophore system in interaction with alveolar macrophages. Microbes Infect 12:1035–1041 [View Article][PubMed]
    [Google Scholar]
  162. Sebulsky M. T., Shilton B. H., Speziali C. D., Heinrichs D. E. 2003; The role of FhuD2 in iron(III)-hydroxamate transport in Staphylococcus aureus. Demonstration that FhuD2 binds iron(III)-hydroxamates but with minimal conformational change and implication of mutations on transport. J Biol Chem 278:49890–49900 [View Article][PubMed]
    [Google Scholar]
  163. Sebulsky M. T., Speziali C. D., Shilton B. H., Edgell D. R., Heinrichs D. E. 2004; FhuD1, a ferric hydroxamate-binding lipoprotein in Staphylococcus aureus: a case of gene duplication and lateral transfer. J Biol Chem 279:53152–53159 [View Article][PubMed]
    [Google Scholar]
  164. Seifert M., Nairz M., Schroll A., Schrettl M., Haas H., Weiss G. 2008; Effects of the Aspergillus fumigatus siderophore systems on the regulation of macrophage immune effector pathways and iron homeostasis. Immunobiology 213:767–778 [View Article][PubMed]
    [Google Scholar]
  165. Shalom G., Shaw J. G., Thomas M. S. 2007; In vivo expression technology identifies a type VI secretion system locus in Burkholderia pseudomallei that is induced upon invasion of macrophages. Microbiology 153:2689–2699 [View Article][PubMed]
    [Google Scholar]
  166. Sheldon J. R., Heinrichs D. E. 2015; Recent developments in understanding the iron acquisition strategies of gram positive pathogens. FEMS Microbiol Rev 39:592–630 [View Article][PubMed]
    [Google Scholar]
  167. Skaar E. P., Gaspar A. H., Schneewind O. 2004a; IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus . J Biol Chem 279:436–443 [View Article][PubMed]
    [Google Scholar]
  168. Skaar E. P., Humayun M., Bae T., DeBord K. L., Schneewind O. 2004b; Iron-source preference of Staphylococcus aureus infections. Science 305:1626–1628 [View Article][PubMed]
    [Google Scholar]
  169. Smith E. E., Buckley D. G., Wu Z., Saenphimmachak C., Hoffman L. R., D'Argenio D. A., Miller S. I., Ramsey B. W., Speert D. P., other authors. 2006; Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci U S A 103:8487–8492 [View Article][PubMed]
    [Google Scholar]
  170. Sokol P. A. 1986; Production and utilization of pyochelin by clinical isolates of Pseudomonas cepacia. J Clin Microbiol 23:560–562
    [Google Scholar]
  171. Sokol P. A., Darling P., Woods D. E., Mahenthiralingam E., Kooi C. 1999; Role of ornibactin biosynthesis in the virulence of Burkholderia cepacia: characterization of pvdA, the gene encoding l-ornithine N 5-oxygenase. Infect Immun 67:4443–4455
    [Google Scholar]
  172. Sokol P. A., Darling P., Lewenza S., Corbett C. R., Kooi C. D. 2000; Identification of a siderophore receptor required for ferric ornibactin uptake in Burkholderia cepacia . Infect Immun 68:6554–6560 [View Article][PubMed]
    [Google Scholar]
  173. Stephan H., Freund S., Beck W., Jung G., Meyer J. M., Winkelmann G. 1993; Ornibactins - a new family of siderophores from Pseudomonas . Biometals 6:93–100 [View Article][PubMed]
    [Google Scholar]
  174. Stites S. W., Walters B., O'Brien-Ladner A. R., Bailey K., Wesselius L. J. 1998; Increased iron and ferritin content of sputum from patients with cystic fibrosis or chronic bronchitis. Chest 114:814–819 [View Article][PubMed]
    [Google Scholar]
  175. Stites S. W., Plautz M. W., Bailey K., O'Brien-Ladner A. R., Wesselius L. J. 1999; Increased concentrations of iron and isoferritins in the lower respiratory tract of patients with stable cystic fibrosis. Am J Respir Crit Care Med 160:796–801 [View Article][PubMed]
    [Google Scholar]
  176. Stojiljkovic I., Perkins-Balding D. 2002; Processing of heme and heme-containing proteins by bacteria. DNA Cell Biol 21:281–295 [View Article][PubMed]
    [Google Scholar]
  177. Stojiljkovic I., Kumar V., Srinivasan N. 1999; Non-iron metalloporphyrins: potent antibacterial compounds that exploit haem/Hb uptake systems of pathogenic bacteria. Mol Microbiol 31:429–442 [View Article][PubMed]
    [Google Scholar]
  178. Stojiljkovic I., Evavold B. D., Kumar V. 2001; Antimicrobial properties of porphyrins. Expert Opin Investig Drugs 10:309–320 [View Article][PubMed]
    [Google Scholar]
  179. Takase H., Nitanai H., Hoshino K., Otani T. 2000; Impact of siderophore production on Pseudomonas aeruginosa infections in immunosuppressed mice. Infect Immun 68:1834–1839 [View Article][PubMed]
    [Google Scholar]
  180. Tanaka W. T., Nakao N., Mikami T., Matsumoto T. 1997; Hemoglobin is utilized by Candida albicans in the hyphal form but not yeast form. Biochem Biophys Res Commun 232:350–353 [View Article][PubMed]
    [Google Scholar]
  181. Tate S., MacGregor G., Davis M., Innes J. A., Greening A. P. 2002; Airways in cystic fibrosis are acidified: detection by exhaled breath condensate. Thorax 57:926–929 [View Article][PubMed]
    [Google Scholar]
  182. Thomas M. S. 2007; Iron acquisition mechanisms of the Burkholderia cepacia complex. Biometals 20:431–452 [View Article][PubMed]
    [Google Scholar]
  183. Tian F., Ding Y., Zhu H., Yao L., Du B. 2009; Genetic diversity of siderophore-producing bacteria of tobacco rhizosphere. Braz J Microbiol 40:276–284 [View Article][PubMed]
    [Google Scholar]
  184. Tomaras A. P., Crandon J. L., McPherson C. J., Banevicius M. A., Finegan S. M., Irvine R. L., Brown M. F., O'Donnell J. P., Nicolau D. P. 2013; Adaptation-based resistance to siderophore-conjugated antibacterial agents by Pseudomonas aeruginosa . Antimicrob Agents Chemother 57:4197–4207 [View Article][PubMed]
    [Google Scholar]
  185. Tripathi A., Schofield M. M., Chlipala G. E., Schultz P. J., Yim I., Newmister S. A., Nusca T. D., Scaglione J. B., Hanna P. C., other authors. 2014; Baulamycins A and B, broad-spectrum antibiotics identified as inhibitors of siderophore biosynthesis in Staphylococcus aureus and Bacillus anthracis . J Am Chem Soc 136:1579–1586 [View Article][PubMed]
    [Google Scholar]
  186. Tyrrell J., Whelan N., Wright C., Sá-Correia I., McClean S., Thomas M., Callaghan M. 2015; Investigation of the multifaceted iron acquisition strategies of Burkholderia cenocepacia . Biometals 28:367–380 [View Article][PubMed]
    [Google Scholar]
  187. Vaknin Y., Shadkchan Y., Levdansky E., Morozov M., Romano J., Osherov N. 2014; The three Aspergillus fumigatus CFEM-domain GPI-anchored proteins (CfmA-C) affect cell-wall stability but do not play a role in fungal virulence. Fungal Genet Biol 63:55–64 [View Article][PubMed]
    [Google Scholar]
  188. 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 [View Article][PubMed]
    [Google Scholar]
  189. Wallner A., Blatzer M., Schrettl M., Sarg B., Lindner H., Haas H. 2009; Ferricrocin, a siderophore involved in intra- and transcellular iron distribution in Aspergillus fumigatus . Appl Environ Microbiol 75:4194–4196 [View Article][PubMed]
    [Google Scholar]
  190. Wang Y., Wilks J. C., Danhorn T., Ramos I., Croal L., Newman D. K. 2011; Phenazine-1-carboxylic acid promotes bacterial biofilm development via ferrous iron acquisition. J Bacteriol 193:3606–3617 [View Article][PubMed]
    [Google Scholar]
  191. Watanabe T., Takano M., Murakami M., Tanaka H., Matsuhisa A., Nakao N., Mikami T., Suzuki M., Matsumoto T. 1999; Characterization of a haemolytic factor from Candida albicans . Microbiology 145:689–694 [View Article][PubMed]
    [Google Scholar]
  192. Weaver V. B., Kolter R. 2004; Burkholderia spp. alter Pseudomonas aeruginosa physiology through iron sequestration. J Bacteriol 186:2376–2384 [View Article][PubMed]
    [Google Scholar]
  193. Wegele R., Tasler R., Zeng Y., Rivera M., Frankenberg-Dinkel N. 2004; The heme oxygenase(s)-phytochrome system of Pseudomonas aeruginosa . J Biol Chem 279:45791–45802 [View Article][PubMed]
    [Google Scholar]
  194. Weissman Z., Kornitzer D. 2004; A family of Candida cell surface haem-binding proteins involved in haemin and haemoglobin-iron utilization. Mol Microbiol 53:1209–1220 [View Article][PubMed]
    [Google Scholar]
  195. Wencewicz T. A., Möllmann U., Long T. E., Miller M. J. 2009; Is drug release necessary for antimicrobial activity of siderophore-drug conjugates? Syntheses and biological studies of the naturally occurring salmycin Trojan Horse antibiotics and synthetic desferridanoxamine-antibiotic conjugates. Biometals 22:633–648 [View Article][PubMed]
    [Google Scholar]
  196. Whitby P. W., Vanwagoner T. M., Springer J. M., Morton D. J., Seale T. W., Stull T. L. 2006; Burkholderia cenocepacia utilizes ferritin as an iron source. J Med Microbiol 55:661–668 [View Article][PubMed]
    [Google Scholar]
  197. Wiens J. R., Vasil A. I., Schurr M. J., Vasil M. L. 2014; Iron-regulated expression of alginate production, mucoid phenotype, and biofilm formation by Pseudomonas aeruginosa . MBio 5:e01010–e01013 [View Article][PubMed]
    [Google Scholar]
  198. Wilderman P. J., Vasil A. I., Johnson Z., Wilson M. J., Cunliffe H. E., Lamont I. L., Vasil M. L. 2001; Characterization of an endoprotease (PrpL) encoded by a PvdS-regulated gene in Pseudomonas aeruginosa . Infect Immun 69:5385–5394 [View Article][PubMed]
    [Google Scholar]
  199. Wolz C., Hohloch K., Ocaktan A., Poole K., Evans R. W., Rochel N., Albrecht-Gary A. M., Abdallah M. A., Döring G. 1994; Iron release from transferrin by pyoverdin and elastase from Pseudomonas aeruginosa . Infect Immun 62:4021–4027
    [Google Scholar]
  200. Xiong Y. Q., Vasil M. L., Johnson Z., Ochsner U. A., Bayer A. S. 2000; The oxygen- and iron-dependent sigma factor pvdS of Pseudomonas aeruginosa is an important virulence factor in experimental infective endocarditis. J Infect Dis 181:1020–1026 [View Article][PubMed]
    [Google Scholar]
  201. Yin W. B., Baccile J. A., Bok J. W., Chen Y., Keller N. P., Schroeder F. C. 2013; A nonribosomal peptide synthetase-derived iron(III) complex from the pathogenic fungus Aspergillus fumigatus . J Am Chem Soc 135:2064–2067 [View Article][PubMed]
    [Google Scholar]
  202. Yu Q., Dong Y., Xu N., Qian K., Chen Y., Zhang B., Xing L., Li M. 2014; A novel role of the ferric reductase Cfl1 in cell wall integrity, mitochondrial function, and invasion to host cells in Candida albicans . FEMS Yeast Res 14:1037–1047 [CrossRef]
    [Google Scholar]
  203. Zeng Y., Kulkarni A., Yang Z., Patil P. B., Zhou W., Chi X., Van Lanen S., Chen S. 2012; Biosynthesis of albomycin δ2 provides a template for assembling siderophore and aminoacyl-tRNA synthetase inhibitor conjugates. ACS Chem Biol 7:1565–1575 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.000220
Loading
/content/journal/micro/10.1099/mic.0.000220
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error