, Volume 173, Issue 5–6, pp 451–461 | Cite as

Pseudomonas aeruginosa Inhibits the Growth of Cryptococcus Species

  • Antonella Rella
  • Mo Wei Yang
  • Jordon Gruber
  • Maria Teresa Montagna
  • Chiara Luberto
  • Yong-Mei Zhang
  • Maurizio Del Poeta


Pseudomonas aeruginosa is a ubiquitous and opportunistic bacterium that inhibits the growth of different microorganisms, including Gram-positive bacteria and fungi such as Candida spp. and Aspergillus fumigatus. In this study, we investigated the interaction between P. aeruginosa and Cryptococcus spp. We found that P. aeruginosa PA14 and, to a lesser extent, PAO1 significantly inhibited the growth of Cryptococcus spp. The inhibition of growth was observed on solid medium by the visualization of a zone of inhibition of yeast growth and in liquid culture by viable cell counting. Interestingly, such inhibition was only observed when P. aeruginosa and Cryptococcus were co-cultured. Minimal inhibition was observed when cell–cell contact was prevented using a separation membrane, suggesting that cell contact is required for inhibition. Using mutant strains of Pseudomonas quinoline signaling, we showed that P. aeruginosa inhibited the growth of Cryptococcus spp. by producing antifungal molecules pyocyanin, a redox-active phenazine, and 2-heptyl-3,4-dihydroxyquinoline (PQS), an extracellular quorum-sensing signal. Because both P. aeruginosa and Cryptococcus neoformans are commonly found in lung infections of immunocompromised patients, this study may have important implication for the interaction of these microbes in both an ecological and a clinical point of view.


Cryptococcus spp. Pseudomonas aeruginosa Quorum sensing 2-heptyl-3,4-dihydroxyquinoline Pyocyanin 



We thank all members of Del Poeta, Zhang and Luberto laboratories for discussion. This work was supported in part by Grants AI56168, AI71142, AI78493 and AI87541 (to M.D.P) from the National Institute of Health, in part by RR17677 (to M. D. P. and Y-M. Z) from the Centers of Biomedical Research Excellence Program of the National Center for Research Resources, and in part by NIH C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources. Dr. Maurizio Del Poeta is a Burroughs Wellcome New Investigator in the Pathogenesis of Infectious Diseases.


  1. 1.
    Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am 2006;20(3):507–544, v–vi. doi: 10.1016/j.idc.2006.07.001.
  2. 2.
    Fraser JA, Giles SS, Wenink EC, Geunes-Boyer SG, Wright JR, Diezmann S, et al. Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak. Nature. 2005;437(7063):1360–4. doi: 10.1038/nature04220.PubMedCrossRefGoogle Scholar
  3. 3.
    Mansour MK, Levitz SM. Interactions of fungi with phagocytes. Curr Opin Microbiol. 2002;5(4):359–65.PubMedCrossRefGoogle Scholar
  4. 4.
    Feldmesser M, Tucker S, Casadevall A. Intracellular parasitism of macrophages by Cryptococcus neoformans. Trends Microbiol. 2001;9(6):273–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Levitz SM, Nong SH, Seetoo KF, Harrison TS, Speizer RA, Simons ER. Cryptococcus neoformans resides in an acidic phagolysosome of human macrophages. Infect Immun. 1999;67(2):885–90.PubMedGoogle Scholar
  6. 6.
    Chretien F, Lortholary O, Kansau I, Neuville S, Gray F, Dromer F. Pathogenesis of cerebral Cryptococcus neoformans infection after fungemia. J Infect Dis. 2002;186(4):522–30. doi: 10.1086/341564.PubMedCrossRefGoogle Scholar
  7. 7.
    Maschmeyer G, Braveny I. Review of the incidence and prognosis of Pseudomonas aeruginosa infections in cancer patients in the 1990s. Eur J Clin Microbiol Infect Dis. 2000;19(12):915–25.PubMedCrossRefGoogle Scholar
  8. 8.
    Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(1):1–12. doi: 10.1086/595011.PubMedCrossRefGoogle Scholar
  9. 9.
    Gibson J, Sood A, Hogan DA. Pseudomonas aeruginosa-Candida albicans interactions: localization and fungal toxicity of a phenazine derivative. Appl Environ Microbiol. 2009;75(2):504–13. doi: 10.1128/AEM.01037-08.PubMedCrossRefGoogle Scholar
  10. 10.
    Kerr J. Inhibition of fungal growth by Pseudomonas aeruginosa and Pseudomonas cepacia isolated from patients with cystic fibrosis. J Infect. 1994;28(3):305–10.PubMedCrossRefGoogle Scholar
  11. 11.
    Kerr JR, Taylor GW, Rutman A, Hoiby N, Cole PJ, Wilson R. Pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine inhibit fungal growth. J Clin Pathol. 1999;52(5):385–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Fisher AM. Inhibition of growth of Cryptococcus neoformans by cultures of Pseudomonas aeruginosa. Bull Johns Hopkins Hosp. 1954;95(4):157–61.PubMedGoogle Scholar
  13. 13.
    Teoh-Chan H, Chau PY, Ng MH, Wong PC. Inhibition of Cryptococcus neoformans by Pseudomonas aeruginosa. J Med Microbiol. 1975;8(1):77–81.PubMedCrossRefGoogle Scholar
  14. 14.
    Choi JY, Sifri CD, Goumnerov BC, Rahme LG, Ausubel FM, Calderwood SB. Identification of virulence genes in a pathogenic strain of Pseudomonas aeruginosa by representational difference analysis. J Bacteriol. 2002;184(4):952–61.PubMedCrossRefGoogle Scholar
  15. 15.
    Tan MW, Mahajan-Miklos S, Ausubel FM. Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci USA. 1999;96(2):715–20.PubMedCrossRefGoogle Scholar
  16. 16.
    Choi KH, Schweizer HP. An improved method for rapid generation of unmarked Pseudomonas aeruginosa deletion mutants. BMC Microbiol. 2005;5:30. doi: 10.1186/1471-2180-5-30.PubMedCrossRefGoogle Scholar
  17. 17.
    Tully JG Jr, Latteri A. Paraplegia, syringomyelia tarda and neuropathic arthrosis of the shoulder: a triad. Clin Orthop Relat Res. 1978;134:244–8.PubMedGoogle Scholar
  18. 18.
    Heeb S, Fletcher MP, Chhabra SR, Diggle SP, Williams P, Camara M. Quinolones: from antibiotics to autoinducers. FEMS Microbiol Rev. 2011;35(2):247–74. doi: 10.1111/j.1574-6976.2010.00247.x.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang YM, Frank MW, Zhu K, Mayasundari A, Rock CO. PqsD is responsible for the synthesis of 2, 4-dihydroxyquinoline, an extracellular metabolite produced by Pseudomonas aeruginosa. J Biol Chem. 2008;283(43):28788–94. doi: 10.1074/jbc.M804555200.PubMedCrossRefGoogle Scholar
  20. 20.
    Machan ZA, Taylor GW, Pitt TL, Cole PJ, Wilson R. 2-Heptyl-4-hydroxyquinoline N-oxide, an antistaphylococcal agent produced by Pseudomonas aeruginosa. J Antimicrob Chemother. 1992;30(5):615–23.PubMedCrossRefGoogle Scholar
  21. 21.
    Mowat E, Rajendran R, Williams C, McCulloch E, Jones B, Lang S, et al. Pseudomonas aeruginosa and their small diffusible extracellular molecules inhibit Aspergillus fumigatus biofilm formation. FEMS Microbiol Lett. 2010;313(2):96–102. doi: 10.1111/j.1574-6968.2010.02130.x.PubMedCrossRefGoogle Scholar
  22. 22.
    Holloway BW. Genetic recombination in Pseudomonas aeruginosa. J Gen Microbiol. 1955;13(3):572–81.PubMedGoogle Scholar
  23. 23.
    Rahme LG, Stevens EJ, Wolfort SF, Shao J, Tompkins RG, Ausubel FM. Common virulence factors for bacterial pathogenicity in plants and animals. Science. 1995;268(5219):1899–902.PubMedCrossRefGoogle Scholar
  24. 24.
    Lee DG, Urbach JM, Wu G, Liberati NT, Feinbaum RL, Miyata S et al. Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial. Genome Biol. 2006;7(10):R90. doi: 10.1186/gb-2006-7-10-r90.
  25. 25.
    Hogan DA, Kolter R. Pseudomonas-Candida interactions: an ecological role for virulence factors. Science. 2002;296(5576):2229–32. doi: 10.1126/science.1070784.PubMedCrossRefGoogle Scholar
  26. 26.
    Singh A, Del Poeta M. Lipid signalling in pathogenic fungi. Cell Microbiol. 2011;13(2):177–85. doi: 10.1111/j.1462-5822.2010.01550.x.PubMedCrossRefGoogle Scholar
  27. 27.
    Oliver A. Mutators in cystic fibrosis chronic lung infection: prevalence, mechanisms, and consequences for antimicrobial therapy. Int J Med Microbiol. 2010;300(8):563–72. doi: 10.1016/j.ijmm.2010.08.009.PubMedCrossRefGoogle Scholar
  28. 28.
    Hoboth C, Hoffmann R, Eichner A, Henke C, Schmoldt S, Imhof A, et al. Dynamics of adaptive microevolution of hypermutable Pseudomonas aeruginosa during chronic pulmonary infection in patients with cystic fibrosis. J Infect Dis. 2009;200(1):118–30. doi: 10.1086/599360.PubMedCrossRefGoogle Scholar
  29. 29.
    Bakare N, Rickerts V, Bargon J, Just-Nubling G. Prevalence of Aspergillus fumigatus and other fungal species in the sputum of adult patients with cystic fibrosis. Mycoses. 2003;46(1–2):19–23.PubMedCrossRefGoogle Scholar
  30. 30.
    Hughes WT, Kim HK. Mycoflora in cystic fibrosis: some ecologic aspects of Pseudomonas aeruginosa and Candida albicans. Mycopathol Mycol Appl. 1973;50(3):261–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Taylor GW, Machan ZA, Mehmet S, Cole PJ, Wilson R. Rapid identification of 4-hydroxy-2-alkylquinolines produced by Pseudomonas aeruginosa using gas chromatography-electron-capture mass spectrometry. J Chromatogr B Biomed Appl. 1995;664(2):458–62.PubMedCrossRefGoogle Scholar
  32. 32.
    Caldwell CC, Chen Y, Goetzmann HS, Hao Y, Borchers MT, Hassett DJ, et al. Pseudomonas aeruginosa exotoxin pyocyanin causes cystic fibrosis airway pathogenesis. Am J Pathol. 2009;175(6):2473–88. doi: 10.2353/ajpath.2009.090166.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Antonella Rella
    • 1
    • 5
  • Mo Wei Yang
    • 1
  • Jordon Gruber
    • 1
  • Maria Teresa Montagna
    • 5
  • Chiara Luberto
    • 1
  • Yong-Mei Zhang
    • 1
    • 2
  • Maurizio Del Poeta
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of Biochemistry and Molecular BiologyMedical University of South CarolinaCharlestonUSA
  2. 2.Department of Microbiology and ImmunologyMedical University of South CarolinaCharlestonUSA
  3. 3.Department of Craniofacial BiologyMedical University of South CarolinaCharlestonUSA
  4. 4.Division of Infectious DiseasesMedical University of South CarolinaCharlestonUSA
  5. 5.Department of Biomedical Science and Human OncologyHygiene Section, University of BariBariItaly

Personalised recommendations