scholarly journals A Small Subpopulation of Blastospores in Candida albicans Biofilms Exhibit Resistance to Amphotericin B Associated with Differential Regulation of Ergosterol and β-1,6-Glucan Pathway Genes

2006 ◽  
Vol 50 (11) ◽  
pp. 3708-3716 ◽  
Author(s):  
Prasanna D. Khot ◽  
Peter A. Suci ◽  
R. Lance Miller ◽  
Raoul D. Nelson ◽  
Bonnie J. Tyler
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Transcript Abundance ◽  
Differential Regulation ◽  
Morphological Heterogeneity ◽  
Tubular Flow ◽  
High Level ◽  
Candida Albicans Biofilms ◽  
Small Subpopulation

ABSTRACT The resistance of Candida albicans biofilms to a broad spectrum of antimicrobial agents has been well documented. Biofilms are known to be heterogeneous, consisting of microenvironments that may induce formation of resistant subpopulations. In this study we characterized one such subpopulation. C. albicans biofilms were cultured in a tubular flow cell (TF) for 36 h. The relatively large shear forces imposed by draining the TF removed most of the biofilm, which consisted of a tangled mass of filamentous forms with associated clusters of yeast forms. This portion of the biofilm exhibited the classic architecture and morphological heterogeneity of a C. albicans biofilm and was only slightly more resistant than either exponential- or stationary-phase planktonic cells. A submonolayer fraction of blastospores that remained on the substratum was resistant to 10 times the amphotericin B dose that eliminated the activity of the planktonic populations. A comparison between planktonic and biofilm populations of transcript abundance for genes coding for enzymes in the ergosterol (ERG1, -3, -5, -6, -9, -11, and -25) and β-1,6-glucan (SKN and KRE1, -5, -6, and -9) pathways was performed by quantitative RT-PCR. The results indicate a possible association between the high level of resistance exhibited by the blastospore subpopulation and differential regulation of ERG1, ERG25, SKN1, and KRE1. We hypothesize that the resistance originates from a synergistic effect involving changes in both the cell membrane and the cell wall.

scholarly journals Transcriptional response to fluconazole and amphotericin B in Candida albicans biofilms

2010 ◽  
Vol 161 (4) ◽  
pp. 284-292 ◽  
Author(s):  
Heleen Nailis ◽  
Davy Vandenbosch ◽  
Dieter Deforce ◽  
Hans J. Nelis ◽  
Tom Coenye
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Transcriptional Response ◽  
Candida Albicans Biofilms

P1956 In vitro activity of amphotericin B and anidulafungin against Candida albicans biofilms

2007 ◽  
Vol 29 ◽  
pp. S562
Author(s):  
A. Valentín ◽  
E. Cantóon ◽  
J. Pemáan ◽  
M. Bosch ◽  
E. Eraso ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Albicans Biofilms

scholarly journals In Vitro Pharmacodynamic Properties of Three Antifungal Agents against Preformed Candida albicans Biofilms Determined by Time-Kill Studies

2002 ◽  
Vol 46 (11) ◽  
pp. 3634-3636 ◽  
Author(s):  
Gordon Ramage ◽  
Kacy VandeWalle ◽  
Stefano P. Bachmann ◽  
Brian L. Wickes ◽  
José L. López-Ribot
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Pharmacokinetic Properties ◽  
Time Kill ◽  
Candida Albicans Biofilms

ABSTRACT We have examined the in vitro activities of fluconazole, amphotericin B, and caspofungin against Candida albicans biofilms by time-kill methodology. Fluconazole was ineffective against biofilms. Killing of biofilm cells was suboptimal at therapeutic concentrations of amphotericin B. Caspofungin displayed the most effective pharmacokinetic properties, with ≥99% killing at physiological concentrations.

Candida albicans biofilms formed into catheters and probes and their resistance to amphotericin B

2011 ◽  
Vol 21 (3) ◽  
pp. 182-187 ◽  
Author(s):  
Z. Boucherit-Atmani ◽  
S.M.L. Seddiki ◽  
K. Boucherit ◽  
L. Sari-Belkharoubi ◽  
D. Kunkel
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Candida Albicans Biofilms

scholarly journals In VitroInteractions between Aspirin and Amphotericin B against Planktonic Cells and Biofilm Cells of Candida albicans and C. parapsilosis

2012 ◽  
Vol 56 (6) ◽  
pp. 3250-3260 ◽  
Author(s):  
Yabin Zhou ◽  
Ganggang Wang ◽  
Yutang Li ◽  
Yang Liu ◽  
Yu Song ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Positive Interactions ◽  
Antibiofilm Activity ◽  
Data Generation ◽  
Planktonic Cells ◽  
Content Type ◽  
Time Kill

ABSTRACTThe increase in drug resistance and invasion caused by biofilm formation brings enormous challenges to the management ofCandidainfection. Aspirin's antibiofilm activityin vitrowas discovered recently. The spectrophotometric method and the XTT {2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide} reduction assay used for data generation make it possible to evaluate fungal biofilm growth accurately. The combined use of the most commonly used methods, the fractional inhibitory concentration index (FICI) and a newly developed method, the ΔEmodel, which uses the concentration-effect relationship over the whole concentration range instead of using the MIC index alone, makes the interpretation of results more reliable. As an attractive tool for studying the pharmacodynamics of antimicrobial agents, time-kill curves can provide detailed information about antimicrobial efficacy as a function of both time and concentration. In the present study,in vitrointeractions between aspirin (acetylsalicylic acid [ASA]) and amphotericin B (AMB) against planktonic cells and biofilm cells ofCandida albicansandC. parapsilosiswere evaluated by the checkerboard microdilution method and the time-kill test. Synergistic and indifferent effects were found for the combination of ASA and AMB against planktonic cells, while strong synergy was found against biofilm cells analyzed by FICI. The ΔEmodel gave more consistent results with FICI. The positive interactions in concentration were also confirmed by the time-kill test. Moreover, this approach also revealed the pharmacodynamics changes of ASA and synergistic action on time. Our findings suggest a potential clinical use for combination therapy with ASA and AMB to augment activity against biofilm-associated infections.

scholarly journals Inhibition of Nucleic Acid Biosynthesis Makes Little Difference to Formation of Amphotericin B-Tolerant Persisters in Candida albicans Biofilm

2014 ◽  
Vol 59 (3) ◽  
pp. 1627-1633 ◽  
Author(s):  
Jing Sun ◽  
Xiaohua Liu ◽  
Guangshui Jiang ◽  
Qingguo Qi
Keyword(s):  
Candida Albicans ◽  
Nucleic Acid ◽  
Amphotericin B ◽  
Total Population ◽  
Acid Synthesis ◽  
Persister Cells ◽  
Content Type ◽  
Nucleic Acid Biosynthesis ◽  
Low Levels ◽  
Small Subpopulation

ABSTRACTCandida albicanspersisters constitute a small subpopulation of biofilm cells and play a major role in recalcitrant chronic candidiasis; however, the mechanism underlying persister formation remains unclear. Persisters are often described as dormant, multidrug-tolerant, nongrowing cells. Persister cells are difficult to isolate and study not only due to their low levels inC. albicansbiofilms but also due to their transient, reversible phenotype. In this study, we tried to induce persister formation by inducingC. albicanscells into a dormant state.C. albicanscells were pretreated with 5-fluorocytosine (planktonic cells, 0.8 μg ml−1; biofilm cells, 1 μg ml−1) for 6 h at 37°C, which inhibits nucleic acid and protein synthesis. Biofilms and planktonic cultures of eightC. albicansstrains were surveyed for persisters after amphotericin B treatment (100 μg ml−1for 24 h) and CFU assay. None of the planktonic cultures, with or without 5-fluorocytosine pretreatment, contained persisters. Persister cells were found in biofilms of all testedC. albicansstrains, representing approximately 0.01 to 1.93% of the total population. However, the persister levels were not significantly increased inC. albicansbiofilms pretreated with 5-fluorocytosine. These results suggest that inhibition of nucleic acid synthesis did not seem to increase the formation of amphotericin B-tolerant persisters inC. albicansbiofilms.

scholarly journals Repurposing as a means to increase the activity of amphotericin B and caspofungin against Candida albicans biofilms

2013 ◽  
Vol 69 (4) ◽  
pp. 1035-1044 ◽  
Author(s):  
N. Delattin ◽  
K. De Brucker ◽  
K. Vandamme ◽  
E. Meert ◽  
A. Marchand ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Candida Albicans Biofilms

scholarly journals Patients with Long-Term Oral Carriage Harbor High-Persister Mutants of Candida albicans

2009 ◽  
Vol 54 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Michael D. LaFleur ◽  
Qingguo Qi ◽  
Kim Lewis
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Oral Candidiasis ◽  
Wild Type ◽  
Persister Cells ◽  
Microtiter Plates ◽  
High Concentrations

ABSTRACT Fungal biofilms produce a small number of persister cells which can tolerate high concentrations of fungicidal agents. Persisters form upon attachment to a surface, an important step in the pathogenesis of Candida strains. The periodic application of antimicrobial agents may select for strains with increased levels of persister cells. In order to test this possibility, 150 isolates of Candida albicans and C. glabrata were obtained from cancer patients who were at high risk for the development of oral candidiasis and who had been treated with topical chlorhexidine once a day. Persister levels were measured by exposing biofilms growing in the wells of microtiter plates to high concentrations of amphotericin B and plating for survivors. The persister levels of the isolates varied from 0.2 to 9%, and strains isolated from patients with long-term carriage had high levels of persisters. High-persister strains were isolated from every patient with Candida carriage of more than 8 consecutive weeks but from no patients with transient carriage. All of the high-persister isolates had an amphotericin B MIC that was the same as that for the wild type, indicating that these strains were drug-tolerant rather than drug-resistant mutants. Biofilms of the majority of high-persister strains also showed an increased tolerance to chlorhexidine and had the same MIC for this antimicrobial as the wild type. This study suggests that persister cells are clinically relevant, and antimicrobial therapy selects for high-persister strains in vivo. The drug tolerance of persisters may be a critical but overlooked component responsible for antimicrobial drug failure and relapsing infections.

scholarly journals Antifungal Combinations against Candida albicans Biofilms In Vitro

2003 ◽  
Vol 47 (11) ◽  
pp. 3657-3659 ◽  
Author(s):  
Stefano P. Bachmann ◽  
Gordon Ramage ◽  
Kacy VandeWalle ◽  
Thomas F. Patterson ◽  
Brian L. Wickes ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Antagonistic Effect ◽  
Titration Method ◽  
Time Kill ◽  
Candida Albicans Biofilms ◽  
Checkerboard Titration

ABSTRACT Candida biofilms display increased resistance to most antifungal agents. We have evaluated the efficacy of combinations of fluconazole (FLC), amphotericin B, and caspofungin (CSP) against Candida albicans biofilms in vitro. Indifference was observed for all the combinations of paired antifungal agents when a checkerboard titration method was used. Time-kill experiments revealed an antagonistic effect of high FLC doses with CSP.

Sign in / Sign up

Export Citation Format

Share Document