&lt;em&gt;Candida albicans&lt;/em&gt; Biofilm Development on Medically-relevant Foreign Bodies in a Mouse Subcutaneous Model Followed by Bioluminescence Imaging

Kucharíková, Soňa; Velde, Greetje Vande; Himmelreich, Uwe; Dijck, Patrick Van

doi:10.3791/52239

Cited by 29 publications

(30 citation statements)

References 25 publications

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“…Consecutive scans with acquisition time of 5 min (binning 2) were acquired until maximal signal intensity was reached. The signal was quantified by using Living Image software (version 4.0, Perkin-Elmer) and reported as photon flux per second (p s −1 ) for a rectangular region of interest placed over each five catheters)62.…”

Section: Methodsmentioning

confidence: 99%

The antifungal caspofungin increases fluoroquinolone activity against Staphylococcus aureus biofilms by inhibiting N-acetylglucosamine transferase

et al. 2016

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Biofilms play a major role in Staphylococcus aureus pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the activity of fluoroquinolones (moxifloxacin, delafloxacin) against S. aureus biofilms grown in vitro (96-well plates or catheters) and in vivo (murine model of implanted catheters). The degree of synergy among different clinical isolates is inversely proportional to the expression level of ica operon, the products of which synthesize poly-N-acetyl-glucosamine polymers, a major constituent of biofilm matrix. In vitro, caspofungin inhibits the activity of IcaA, which shares homology with β-1-3-glucan synthase (caspofungin's pharmacological target in fungi). This inhibition destructures the matrix, reduces the concentration and polymerization of exopolysaccharides in biofilms, and increases fluoroquinolone penetration inside biofilms. Our study identifies a bacterial target for caspofungin and indicates that IcaA inhibitors could potentially be useful in the treatment of biofilm-related infections.

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Section: Methodsmentioning

confidence: 99%

The antifungal caspofungin increases fluoroquinolone activity against Staphylococcus aureus biofilms by inhibiting N-acetylglucosamine transferase

et al. 2016

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“…Polyurethane catheters, overnight incubated in bovine serum, were infected with C. albicans or C. glabrata cells (5 × 10 4 cells/mL) in RPMI medium (Kucharikova et al, 2015 ). After an adhesion phase (90 min at 37°C), these catheters were washed and subsequently treated with caspofungin (0.4 μM), HsLin06_18 (0.5 μM), its combination or control treatment (0.5% DMSO) for 24 h, after which the number of cells per individual biofilm was determined by CFU (Kucharikova et al, 2015 ). All experiments were performed in quadruplicate with at least three biological repeats.…”

Section: Methodsmentioning

confidence: 99%

A Linear 19-Mer Plant Defensin-Derived Peptide Acts Synergistically with Caspofungin against Candida albicans Biofilms

et al. 2017

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Public health problems are associated with device-associated biofilm infections, with Candida albicans being the major fungal pathogen. We previously identified potent antibiofilm combination treatment in which the antifungal plant defensin HsAFP1 is co-administered with caspofungin, the preferred antimycotic to treat such infections. In this study, we identified the smallest linear HsAFP1-derived peptide that acts synergistically with caspofungin or anidulafungin against C. albicans as HsLin06_18, a 19-mer peptide derived from the C-terminal part of HsAFP1. The [caspofungin + HsLin06_18] combination significantly reduced in vitro biofilm formation of Candida glabrata and C. albicans on catheters, as well as biofilm formation of a caspofungin-resistant C. albicans strain. The [caspofungin + HsLin06_18] combination was not cytotoxic and reduced biofilm formation of C. albicans in vivo using a subcutaneous rat catheter model, as compared to control treatment. Mode of action research on the [caspofungin + HsLin06_18] combination pointed to caspofungin-facilitated HsLin06_18 internalization and immediate membrane permeabilization. All these findings point to broad-spectrum antibiofilm activity of a combination of HsLin06_18 and caspofungin.

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“…Mice were anesthetized as previously described (5). In order to compare bioluminescence from the WT control strain and the bioluminescent strain in a single animal, two small incisions were made, one on the left and one on the right side of the back of a mouse, as previously demonstrated (22). Three catheter pieces seeded with the WT strain were implanted on the left, and 3 catheters infected with the bioluminescent strain were inserted on the right side of the back.…”

Section: Fig 4 Legend (Continued)mentioning

confidence: 99%

“…In vivo BLI. Isoflurane anesthesia and the BLI procedure were performed as described before (13,22). Prior to BLI, fresh D-luciferin solution (33.3 mg/ml) was dissolved in sterile saline (0.9% NaCl).…”

Section: Fig 4 Legend (Continued)mentioning

confidence: 99%

Monitoring of Fluconazole and Caspofungin Activity against In Vivo Candida glabrata Biofilms by Bioluminescence Imaging

Persyn

Rogiers

Brock

et al. 2019

Antimicrob Agents Chemother

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Candida glabrata can attach to various medical implants and forms thick biofilms despite its inability to switch from yeast to hyphae. The current in vivo C. glabrata biofilm models only provide limited information about colonization and infection and usually require animal sacrifice. To gain real-time information from individual BALB/c mice, we developed a noninvasive imaging technique to visualize C. glabrata biofilms in catheter fragments that were subcutaneously implanted on the back of mice. Bioluminescent C. glabrata reporter strains (lucOPT 7/2/4 and lucOPT 8/1/4), free of auxotrophic markers, expressing a codon-optimized firefly luciferase were generated. A murine subcutaneous model was used to follow real-time in vivo biofilm formation in the presence and absence of fluconazole and caspofungin. The fungal load in biofilms was quantified by CFU counts and by bioluminescence imaging (BLI). C. glabrata biofilms formed within the first 24 h, as documented by the increased number of device-associated cells and elevated bioluminescent signal compared with adhesion at the time of implant. The in vivo model allowed monitoring of the antibiofilm activity of caspofungin against C. glabrata biofilms through bioluminescent imaging from day four after the initiation of treatment. Contrarily, signals emitted from biofilms implanted in fluconazole-treated mice were similar to the light emitted from control-treated mice. This study gives insights into the real-time development of C. glabrata biofilms under in vivo conditions. BLI proved to be a dynamic, noninvasive, and sensitive tool to monitor continuous biofilm formation and activity of antifungal agents against C. glabrata biofilms formed on abiotic surfaces in vivo.

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<em>Candida albicans</em> Biofilm Development on Medically-relevant Foreign Bodies in a Mouse Subcutaneous Model Followed by Bioluminescence Imaging

Cited by 29 publications

References 25 publications

The antifungal caspofungin increases fluoroquinolone activity against Staphylococcus aureus biofilms by inhibiting N-acetylglucosamine transferase

The antifungal caspofungin increases fluoroquinolone activity against Staphylococcus aureus biofilms by inhibiting N-acetylglucosamine transferase

A Linear 19-Mer Plant Defensin-Derived Peptide Acts Synergistically with Caspofungin against Candida albicans Biofilms

Monitoring of Fluconazole and Caspofungin Activity against In Vivo Candida glabrata Biofilms by Bioluminescence Imaging

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