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Antimicrobial Agents and Chemotherapy, March 2006, p. 1021-1033, Vol. 50, No. 3
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.3.1021-1033.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Susceptibility of Cryptococcus neoformans Biofilms to Antifungal Agents In Vitro

Luis R. Martinez and Arturo Casadevall*

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York

Received 20 September 2005/ Returned for modification 22 October 2005/ Accepted 3 December 2005

Microbial biofilms contribute to virulence and resistance to antibiotics by shielding microbial cells from host defenses and antimicrobial drugs, respectively. Cryptococcus neoformans was demonstrated to form biofilms in polystyrene microtiter plates. The numbers of CFU of disaggregated biofilms, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide reduction, and light and confocal microscopy were used to measure the fungal mass, the metabolic activity, and the appearance of C. neoformans biofilms, respectively. Biofilm development by C. neoformans followed a standard sequence of events: fungal surface attachment, microcolony formation, and matrix production. The susceptibilities of C. neoformans cells of the biofilm and planktonic phenotypes to four antifungal agents were examined. The exposure of C. neoformans cells or preformed cryptococcal biofilms to fluconazole or voriconazole did not result in yeast growth inhibition and did not affect the metabolic activities of the biofilms, respectively. In contrast, both C. neoformans cells and preformed biofilms were susceptible to amphotericin B and caspofungin. However, C. neoformans biofilms were significantly more resistant to amphotericin B and caspofungin than planktonic cells, and their susceptibilities to these drugs were further reduced if cryptococcal cells contained melanin. A spot enzyme-linked immunosorbent assay and light and confocal microscopy were used to investigate how antifungal drugs affected C. neoformans biofilm formation. The mechanism by which amphotericin B and caspofungin interfered with C. neoformans biofilm formation involved capsular polysaccharide release and adherence. Our results suggest that biofilm formation may diminish the efficacies of some antifungal drugs during cryptococcal infection.

* Corresponding author. Mailing address: Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-2215. Fax: (718) 430-8968. E-mail: casadeva{at}aecom.yu.edu.

Antimicrobial Agents and Chemotherapy, March 2006, p. 1021-1033, Vol. 50, No. 3
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.3.1021-1033.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Robertson, E. J., Casadevall, A. (2009). Antibody-Mediated Immobilization of Cryptococcus neoformans Promotes Biofilm Formation. Appl. Environ. Microbiol. 75: 2528-2533 [Abstract] [Full Text]  
  • Cowen, L. E., Steinbach, W. J. (2008). Stress, Drugs, and Evolution: the Role of Cellular Signaling in Fungal Drug Resistance. Eukaryot Cell 7: 747-764 [Full Text]  
  • Martinez, L. R., Casadevall, A. (2007). Cryptococcus neoformans Biofilm Formation Depends on Surface Support and Carbon Source and Reduces Fungal Cell Susceptibility to Heat, Cold, and UV Light. Appl. Environ. Microbiol. 73: 4592-4601 [Abstract] [Full Text]  
  • Nosanchuk, J. D., Casadevall, A. (2006). Impact of Melanin on Microbial Virulence and Clinical Resistance to Antimicrobial Compounds. Antimicrob. Agents Chemother. 50: 3519-3528 [Full Text]  
  • Martinez, L. R., Casadevall, A. (2006). Cryptococcus neoformans Cells in Biofilms Are Less Susceptible than Planktonic Cells to Antimicrobial Molecules Produced by the Innate Immune System.. Infect. Immun. 74: 6118-6123 [Abstract] [Full Text]  
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