Journal Article

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Antimicrobial Agents and Chemotherapy

Antimicrob.Agents Chemother.

Mar

50

3

1021

1033

LR: 20141120; GR: AI033142-11/AI/NIAID NIH HHS/United States; GR: AI033774-11/AI/NIAID NIH HHS/United States; GR: HL059842-08/HL/NHLBI NIH HHS/United States; JID: 0315061; 0 (Antifungal Agents); 0 (Echinocandins); 0 (Formazans); 0 (Melanins); 0 (Peptides,

United States

0066-4804; 0066-4804

PMID: 16495265

eng

Comparative Study; Journal Article; Research Support, N.I.H., Extramural; IM

50/3/1021 [pii]

Unknown(0)

16495265

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.

Amphotericin B/metabolism/pharmacology, Antifungal Agents/metabolism/pharmacology, Biofilms/drug effects, Biomass, Cryptococcus neoformans/cytology/drug effects/metabolism, Dose-Response Relationship, Drug, Echinocandins, Enzyme-Linked Immunosorbent Assay, Fluconazole/metabolism/pharmacology, Formazans/analysis, Melanins/metabolism, Microbial Sensitivity Tests, Microscopy, Confocal, Peptides, Cyclic/metabolism/pharmacology, Plankton/cytology/drug effects/metabolism, Pyrimidines/metabolism/pharmacology, Triazoles/metabolism/pharmacology, Voriconazole

Martinez,L. R., Casadevall,A.

Department of Medicine and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461, USA.

PMC1426450

http://vp9py7xf3h.search.serialssolutions.com/?charset=utf-8&pmid=16495265

2006