Methodologies for in vitro and in vivo evaluation of efficacy of antifungal and antibiofilm agents and surface coatings against fungal biofilms

Dijck, Patrick Van; Sjollema, Jelmer; Cammue, Bruno P. A.; Lagrou, Katrien; Berman, Judith; d’Enfert, Christophe; Andes, David R.; Arendrup, Maiken Cavling; Brakhage, Axel A.; Calderone, Richard; Cantón, Emilia; Coenye, Tom; Cos, Paul; Cowen, Leah E.; Edgerton, Mira; Espinel-Ingroff, Ana; Filler, Scott G.; Ghannoum, Mahmoud; Gow, Neil A. R.; Haas, Hubertus; Jabra‐Rizk, Mary Ann; Johnson, Elizabeth; Lockhart, Shawn R.; Lopez-Ribot, José L.; Maertens, Johan; Munro, Carol A.; Nett, Jeniel E.; Nobile, Clarissa J.; Pfaller, Michael A.; Ramage, Gordon; Sanglard, Dominique; Sanguinetti, Maurizio; Spriet, Isabel; Verweij, Paul E.; Warris, Adilia; Wauters, Joost; Yeaman, Michael R.; Zaat, Sebastian A. J.; Thevissen, Karin

doi:10.15698/mic2018.07.638

Cited by 98 publications

(80 citation statements)

References 317 publications

(267 reference statements)

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“…The tested concentration ranges were the same as described above for biofilm MIC determination. FICIs was calculated using the following formula: ΣFIC = FIC A + FIC B = MIC A comb /MIC A alone + MIC B comb /MIC B alone , where MIC A alone and MIC B alone stand for MICs of drugs A and B when used alone, and MIC A comb and MIC B comb represent the MIC values of drugs A and B in combination at isoeffective combinations respectively (Kovács et al ; Van Dijck et al ). FICI was determined as the lowest ΣFIC.…”

Section: Methodsmentioning

confidence: 99%

Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms

Kovács

Nagy

Tóth

et al. 2019

Lett Appl Microbiol

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Antifungal lock therapy has received significant interest in the last few years because the frequently usage of intravascular devices is associated with an increasing number of catheter‐related bloodstream infections caused by Candida species. Antifungal combinations with synergistic interaction can be a good choice for antifungal lock therapy; therefore, interactions were examined between two echinocandins (caspofungin and micafungin) and the chitin synthesis inhibitor nikkomycin Z against Candida albicans and C. parapsilosis biofilms. Susceptibility was evaluated using the XTT‐based checkerboard microdilution method, while the nature of interactions was assessed by calculating fractional inhibitory concentration indices and using the Bliss independence model. Mathematic‐based evaluations were supplemented with fluorescent LIVE/DEAD viability assay. The results obtained by statistical interaction analyses correlated well with the viability assay. The tested echinocandins with nikkomycin Z caused an extended cell death and the structure of the biofilm was sparse compared to the control, especially for C. albicans. The findings support the simultaneous usage of nikkomycin Z and caspofungin or micafungin in alternative therapies such as the antifungal lock therapy. Significance and Impact of the Study Antifungal lock therapy can be a potential therapeutic approach to eradicate the intraluminal Candida biofilms; however, there is no approved lock strategy against fungal species so far. The results of this study provide valuable evidence that nikkomycin Z acts synergistically in combination with caspofungin or micafungin against biofilms. In addition, this synergy was more pronounced for micafungin combined with nikkomycin Z. Therefore, nikkomycin Z can be considered as a potential agent in antifungal lock therapy especially with micafungin against C. albicans or C. parapsilosis biofilms.

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Section: Methodsmentioning

confidence: 99%

Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms

Kovács

Nagy

Tóth

et al. 2019

Lett Appl Microbiol

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“…Candida albicans was among the pathogens synergistically inhibited by the quinine + bicarbonate/hygromycin combinations. This organism’s ability to form drug-resistant biofilms has been associated with high mortality rates in infected, immunocompromised patients ( Silva et al, 2017 ; Van Dijck et al, 2018 ). We tested the effect of both of the new combinations against fungal metabolic activity within biofilms.…”

Section: Resultsmentioning

confidence: 99%

“…Compared to antibacterial treatments, the current arsenal of approved agents for the treatment of fungal infections is limited, with only four classes of antifungal compound targeting different structures or pathways. Their efficacy is eroded by toxicity or drug resistance ( Vandeputte et al, 2012 ; Delarze and Sanglard, 2015 ; Van Dijck et al, 2018 ). The paucity of current treatments can be explained partly by the common eukaryotic nature of fungal pathogens and their hosts.…”

Section: Introductionmentioning

confidence: 99%

Novel Combinations of Agents Targeting Translation That Synergistically Inhibit Fungal Pathogens

et al. 2018

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A range of fungicides or antifungals are currently deployed to control fungi in agriculture or medicine, but resistance to current agents is growing so new approaches and molecular targets are urgently needed. Recently, different aminoglycoside antibiotics combined with particular transport inhibitors were found to produce strong, synergistic growth-inhibition of fungi, by synergistically increasing the error rate of mRNA translation. Here, focusing on translation fidelity as a novel target for combinatorial antifungal treatment, we tested the hypothesis that alternative combinations of agents known to affect the availability of functional amino acids would synergistically inhibit growth of major fungal pathogens. We screened 172 novel combinations against three phytopathogens (Rhizoctonia solani, Zymoseptoria tritici, and Botrytis cinerea) and three human pathogens (Cryptococcus neoformans, Candida albicans, and Aspergillus fumigatus), showing that 48 combinations inhibited strongly the growth of the pathogens; the growth inhibition effect was significantly greater with the agents combined than by a simple product of their individual effects at the same doses. Of these, 23 combinations were effective against more than one pathogen, including combinations comprising food-and-drug approved compounds, e.g., quinine with bicarbonate, and quinine with hygromycin. These combinations [fractional inhibitory combination (FIC) index ≤0.5] gave up to 100% reduction of fungal growth yield at concentrations of agents which, individually, had negligible effect. No synergy was evident against bacterial, plant or mammalian cells, indicating specificity for fungi. Mode-of-action analyses for quinine + hygromycin indicated that synergistic mistranslation was the antifungal mechanism. That mechanism was not universal as bicarbonate exacerbated quinine action by increasing drug uptake. The study unveils chemical combinations and a target process with potential for control of diverse fungal pathogens, and suggests repurposing possibilities for several current therapeutics.

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“…The plates were then incubated in the dark at 37 °C for 2 h followed by spectrophotometric analysis at 492 nm (Multiskan FC microplate photometer; Thermo Fisher Scientific, Waltham, MA, USA). The lowest concentrations associated with a ≥ 50% and > 90% reduction compared to the control well represented the SMIC 50 and SMIC 90 , respectively 40 .…”

Section: Antifungal Susceptibility Of Planktonic Cells and Biofilm Cementioning

confidence: 96%

Novel and potent antimicrobial effects of caspofungin on drug-resistant Candida and bacteria

Sumiyoshi

Miyazaki

Makau

et al. 2020

Sci Rep

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Echinocandins, including caspofungin, micafungin, and anidulafungin, are first-line antifungal agents for the treatment of invasive candidiasis. They exhibit fungicidal activity by inhibiting the synthesis of β-1,3-d-glucan, an essential component of the fungal cell wall. However, they are active only against proliferating fungal cells and unable to completely eradicate fungal cells even after a 24 h drug exposure in standard time-kill assays. Surprisingly, we found that caspofungin, when dissolved in low ionic solutions, had rapid and potent antimicrobial activities against multidrug-resistant (MDR) Candida and bacteria cells even in non-growth conditions. This effect was not observed in 0.9% NaCl or other ion-containing solutions and was not exerted by other echinocandins. Furthermore, caspofungin dissolved in low ionic solutions drastically reduced mature biofilm cells of MDR Candida auris in only 5 min, as well as Candida-bacterial polymicrobial biofilms in a catheter-lock therapy model. Caspofungin displayed ion concentration-dependent conformational changes and intracellular accumulation with increased reactive oxygen species production, indicating a novel mechanism of action in low ionic conditions. Importantly, caspofungin dissolved in 5% glucose water did not exhibit increased toxicity to human cells. This study facilitates the development of new therapeutic strategies in the management of catheter-related biofilm infections.

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Methodologies for in vitro and in vivo evaluation of efficacy of antifungal and antibiofilm agents and surface coatings against fungal biofilms

Cited by 98 publications

References 317 publications

Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms

Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms

Novel Combinations of Agents Targeting Translation That Synergistically Inhibit Fungal Pathogens

Novel and potent antimicrobial effects of caspofungin on drug-resistant Candida and bacteria

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