Turbinmicin inhibits Candida biofilm growth by disrupting fungal vesicle–mediated trafficking

Zhao, Miao; Zhang, Fan; Żarnowski, Robert; Barns, Kenneth J.; Jones, Ryley; Fossen, Jen; Sánchez, Hiram; Rajski, Scott R.; Audhya, Anjon; Bugni, Tim S.; Andes, David R.

doi:10.1172/jci145123

Cited by 41 publications

(37 citation statements)

References 26 publications

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“…Moreover, the same team reported the striking ability of turbinmicin to block biofilm formation. Indeed, turbinmicin acts by disruption of extracellular vesicle delivery during biofilm growth [139]. Turbinmicin revealed as a promising anti-biofilm and antifungal drug [140].…”

Section: Extracts Of Natural Organismsmentioning

confidence: 99%

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

et al. 2021

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Invasive fungal infections represent an expanding threat to public health. During the past decade, a paradigm shift of candidiasis from Candida albicans to non-albicans Candida species has fundamentally increased with the advent of Candida auris. C. auris was identified in 2009 and is now recognized as an emerging species of concern and underscores the urgent need for novel drug development strategies. In this review, we discuss the genomic epidemiology and the main virulence factors of C. auris. We also focus on the different new strategies and results obtained during the past decade in the field of antifungal design against this emerging C. auris pathogen yeast, based on a medicinal chemist point of view. Critical analyses of chemical features and physicochemical descriptors will be carried out along with the description of reported strategies.

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Section: Extracts Of Natural Organismsmentioning

confidence: 99%

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

et al. 2021

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“…Many Candida rely on the vesicular delivery of extracellular matrix components to form extensive biofilms for drug resistance. Turbinmicin is, therefore, particularly promising as an anti-biofilm drug through interference with the assembly of the extracellular matrix: a rat central venous catheter C. albicans biofilm model demonstrated an almost complete elimination of biofilm in turbinmicin treated rats relative to buffer treated controls ( Zhao et al., 2021 ).…”

Section: Novel Therapeutic Options For Candidamentioning

confidence: 99%

“…Turbinmicin demonstrated broad spectrum, fungicidal activity in vitro , including against pan-resistant C. auris , MDR C. glabrata and triazole-resistant Aspergillus fumigatus , with MICs of 0.5 μg/ml or less ( Zhang et al., 2020 ). Furthermore, a combination of fluconazole and turbinmicin was more efficacious at eliminating biofilm than either drug alone, possibly due to turbinmicin disrupting the extracellular matrix sufficiently to render cells more vulnerable to the azole ( Zhao et al., 2021 ). In vitro safety studies in human red blood cells identified that turbinmicin did not trigger haemolysis even at concentrations 1000 times the MIC.…”

Section: Novel Therapeutic Options For Candidamentioning

confidence: 99%

Drug Resistance and Novel Therapeutic Approaches in Invasive Candidiasis

Murphy

Bicanic

2021

Front. Cell. Infect. Microbiol.

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Candida species are the leading cause of invasive fungal infections worldwide and are associated with acute mortality rates of ~50%. Mortality rates are further augmented in the context of host immunosuppression and infection with drug-resistant Candida species. In this review, we outline antifungal drugs already in clinical use for invasive candidiasis and candidaemia, their targets and mechanisms of resistance in clinically relevant Candida species, encompassing not only classical resistance, but also heteroresistance and tolerance. We describe novel antifungal agents and targets in pre-clinical and clinical development, including their spectrum of activity, antifungal target, clinical trial data and potential in treatment of drug-resistant Candida. Lastly, we discuss the use of combination therapy between conventional and repurposed agents as a potential strategy to combat the threat of emerging resistance in Candida.

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“…No significant reduction in the density and in the length of the hyphae were observed [ 161 ]. Zhao et al [ 162 ] showed that turbinmicin, a highly functionalized polycyclic compound isolated from the marine microbiome, completely disrupted extracellular vesicle (EV) delivery, during biofilm growth at 16 µg/mL, and this impaired the subsequent assembly of the biofilm EPM. C. albicans biofilm EVs have a pivotal role in EPM production and biofilm drug resistance [ 163 ].…”

Section: Reported Antibiofilm Activities Of Pure Natural Compoundsmentioning

confidence: 99%

Fungal Biofilms as a Valuable Target for the Discovery of Natural Products That Cope with the Resistance of Medically Important Fungi—Latest Findings

et al. 2021

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The development of new antifungal agents that target biofilms is an urgent need. Natural products, mainly from the plant kingdom, represent an invaluable source of these entities. The present review provides an update (2017–May 2021) on the available information on essential oils, propolis, extracts from plants, algae, lichens and microorganisms, compounds from different natural sources and nanosystems containing natural products with the capacity to in vitro or in vivo modulate fungal biofilms. The search yielded 42 articles; seven involved essential oils, two Brazilian propolis, six plant extracts and one of each, extracts from lichens and algae/cyanobacteria. Twenty articles deal with the antibiofilm effect of pure natural compounds, with 10 of them including studies of the mechanism of action and five dealing with natural compounds included in nanosystems. Thirty-seven manuscripts evaluated Candida spp. biofilms and two tested Fusarium and Cryptococcus spp. Only one manuscript involved Aspergillus fumigatus. From the data presented here, it is clear that the search of natural products with activity against fungal biofilms has been a highly active area of research in recent years. However, it also reveals the necessity of deepening the studies by (i) evaluating the effect of natural products on biofilms formed by the newly emerged and worrisome health-care associated fungi, C. auris, as well as on other non-albicans Candida spp., Cryptococcus sp. and filamentous fungi; (ii) elucidating the mechanisms of action of the most active natural products; (iii) increasing the in vivo testing.

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Turbinmicin inhibits Candida biofilm growth by disrupting fungal vesicle–mediated trafficking

Abstract: The emergence of drug-resistant fungi has prompted an urgent threat alert from the US Centers for Disease Control (CDC). Biofilm assembly

Cited by 41 publications

References 26 publications

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

Drug Resistance and Novel Therapeutic Approaches in Invasive Candidiasis

Fungal Biofilms as a Valuable Target for the Discovery of Natural Products That Cope with the Resistance of Medically Important Fungi—Latest Findings

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