scholarly journals An Antifungal Benzimidazole Derivative Inhibits Ergosterol Biosynthesis and Reveals Novel Sterols

2015 ◽  
Vol 59 (10) ◽  
pp. 6296-6307 ◽  
Author(s):  
Petra Keller ◽  
Christoph Müller ◽  
Isabel Engelhardt ◽  
Ekkehard Hiller ◽  
Karin Lemuth ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Infections ◽  
Transcriptional Profiling ◽  
Benzimidazole Derivative ◽  
Benzimidazole Derivatives ◽  
Ergosterol Biosynthesis ◽  
Screening Assay ◽  
Content Type ◽  
Life Threatening ◽  
A Cell

ABSTRACTFungal infections are a leading cause of morbidity and death for hospitalized patients, mainly because they remain difficult to diagnose and to treat. Diseases range from widespread superficial infections such as vulvovaginal infections to life-threatening systemic candidiasis. For systemic mycoses, only a restricted arsenal of antifungal agents is available. Commonly used classes of antifungal compounds include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapies, significant side effects, and high costs for several antifungals, there is a need for new antifungals in the clinic. In order to expand the arsenal of compounds with antifungal activity, we previously screened a compound library using a cell-based screening assay. A set of novel benzimidazole derivatives, including (S)-2-(1-aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole (EMC120B12), showed high antifungal activity against several species of pathogenic yeasts, includingCandida glabrataandCandida krusei(species that are highly resistant to antifungals). In this study, comparative analysis of EMC120B12 versus fluconazole and nocodazole, using transcriptional profiling and sterol analysis, strongly suggested that EMC120B12 targets Erg11p in the ergosterol biosynthesis pathway and not microtubules, like other benzimidazoles. In addition to the marker sterol 14-methylergosta-8,24(28)-dien-3β,6α-diol, indicating Erg11p inhibition, related sterols that were hitherto unknown accumulated in the cells during EMC120B12 treatment. The novel sterols have a 3β,6α-diol structure. In addition to the identification of novel sterols, this is the first time that a benzimidazole structure has been shown to result in a block of the ergosterol pathway.

scholarly journals A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives

2011 ◽  
Vol 55 (10) ◽  
pp. 4789-4801 ◽  
Author(s):  
Anke Burger-Kentischer ◽  
Doris Finkelmeier ◽  
Petra Keller ◽  
Jörg Bauer ◽  
Holger Eickhoff ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Infections ◽  
Transcriptional Profiling ◽  
Benzimidazole Derivative ◽  
Human Cells ◽  
Benzimidazole Derivatives ◽  
Screening Assay ◽  
Content Type ◽  
Culture Models ◽  
Life Threatening

ABSTRACTFungal infections are a serious health problem in clinics, especially in the immune-compromised patient. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses, only a limited arsenal of antifungals is available. The most commonly used classes of antifungal compounds used include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapy, significant side effects, and high costs for several antifungals, there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities, we screened a compound library including more than 35,000 individual compounds derived from organic synthesis as well as combinatorial compound collections representing mixtures of compounds for antimycotic activity. In total, more than 100,000 compounds were screened using a new type of activity-selectivity assay, analyzing both the antifungal activity and the compatibility with human cells at the same time. One promising hit, an (S)-2-aminoalkyl benzimidazole derivative, was developed among a series of lead compounds showing potent antifungal activity. (S)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole showed the highest antifungal activity and the best compatibility with human cells in several cell culture models and against a number of clinical isolates of several species of pathogenicCandidayeasts. Transcriptional profiling indicates that the newly discovered compound is a potential inhibitor of the ergosterol pathway, in contrast to other benzimidazole derivatives, which target microtubules.

Efficacy of Novel Schiff base Derivatives as Antifungal Compounds in Combination with Approved Drugs Against Candida Albicans

2019 ◽  
Vol 15 (6) ◽  
pp. 648-658 ◽  
Author(s):  
Manzoor Ahmad Malik ◽  
Shabir Ahmad Lone ◽  
Parveez Gull ◽  
Ovas Ahmad Dar ◽  
Mohmmad Younus Wani ◽  
...  
Keyword(s):  
Schiff Base ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Fungal Infections ◽  
Total Sterol ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Ergosterol Biosynthesis ◽  
Dependent Manner ◽  
Schiff Base Derivatives

Background: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required. Methods: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates. Results: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies. Conclusion: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds.

scholarly journals Pyridines and Pyrimidines Mediating Activity against an Efflux-Negative Strain of Candida albicans through Putative Inhibition of Lanosterol Demethylase

2004 ◽  
Vol 48 (1) ◽  
pp. 313-318 ◽  
Author(s):  
Ed T. Buurman ◽  
April E. Blodgett ◽  
Kenneth G. Hull ◽  
Daniel Carcanague
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Ergosterol Biosynthesis ◽  
Clear Correlation ◽  
Wild Type ◽  
Inhibition Of Growth ◽  
Ergosterol Synthesis ◽  
A Cell ◽  
Sterol Profile ◽  
Lanosterol Demethylase

ABSTRACT The first step in ergosterol biosynthesis in Saccharomyces cerevisiae consists of the condensation of two acetyl coenzyme A (acetyl-CoA) moieties by acetoacetyl-CoA thiolase, encoded by ERG10. The inhibition of the sterol pathway results in feedback activation of ERG10 transcription. A cell-based reporter assay, in which increased ERG10 transcription results in elevated specific β-galactosidase activity, was used to find novel inhibitors of ergosterol biosynthesis that could serve as chemical starting points for the development of novel antifungal agents. A class of pyridines and pyrimidines identified in this way had no detectable activity against the major fungal pathogen Candida albicans (MICs > 64 μg · ml−1). However, a strain of C. albicans lacking the Cdr1p and Cdr2p efflux pumps was sensitive to the compounds (with MICs ranging from 2 to 64 μg · ml−1), suggesting that they are efficiently removed from wild-type cells. Quantitative analysis of sterol intermediates that accumulated during growth inhibition revealed the accumulation of lanosterol at the expense of ergosterol. Furthermore, a clear correlation was found between the 50% inhibitory concentration at which the sterol profile was altered and the antifungal activity, measured as the MIC. This finding strongly suggests that the inhibition of growth was caused by a reduction in ergosterol synthesis. The compounds described here are a novel class of antifungal pyridines and pyrimidines and the first pyri(mi)dines to be shown to putatively mediate their antifungal activity against C. albicans via lanosterol demethylase.

Synthesis and Antimicrobial Activity of Some New N-(1H-benzimidazol-2- yl)-2-mercaptoacetamide Derivatives

2018 ◽  
Vol 15 (2) ◽  
pp. 154-159
Author(s):  
Asaf Evrim Evren ◽  
Sinem Tekinkoca ◽  
Leyla Yurttas
Keyword(s):  
Antimicrobial Activity ◽  
Antifungal Activity ◽  
Bacterial Resistance ◽  
Fungal Infections ◽  
Antimicrobial Activities ◽  
Benzimidazole Derivatives ◽  
Standard Drug ◽  
E Coli ◽  
Pharmacological Significance ◽  
Anti Fungal

Background: Due to multi-drug, extended-drug, and pandrug resistance phenotypes, bacterial resistance to antibiotics and fungal infections are a general health issue. Particulary, increase of fungal infections due to secondary cause of human diseases have been observed. An extensive variety of benzimidazole derivatives have been characterized for their chemotherapeutic significance. Benzimidazole derivatives have received important attention because of pharmacological significance during current years, especially antimicrobial, anti-fungal, antitubercular, antioxidant, anti-Alzheimer's disease and antihypertension activities. Methods: Some N-(1H-benzimidazol-2-yl)-2-mercaptoacetamide derivatives (2a-h) were synthesised and evaluated for their antimicrobial activity. The title compounds were gained by reacting N-(1H-benzimidazol-2-yl)-2-chloroacetamide with some substituted 2-mercapto heterocyclic rings. The synthesised compounds were investigated for their antimicrobial activities against C. albicans (ATCC 24433), C. krusei (ATCC 6258), C. glabrata (ATCC90030), C. parapsilosis (ATCC 22019), E. coli (ATCC 25922), E. coli (ATCC 35218), E. feacalis (ATCC 51299), E. feacalis (ATCC 29212), S. aureus (ATCC 25923), K. pneumoniae (ATCC 700603), P. aeruginosa (ATCC 27853). Results: The compounds showed high antifungal activity when compared with standard drug ketoconazole. In addition, all compounds (MIC 100 µg/mL) showed inhibitor activity against P. aeruginosa at two fold concentration of chloramphenicol (MIC 50 µg/mL). Also, compounds 2a, 2c and 2e (MIC: 50 µg/mL) have equal effect against E. coli (ATCC 35218) and more effective than other compounds (MIC of chloramphenicol: 100 µg/mL). Conclusıon: All compounds showed notable activity. Compounds have determined to possess higher antifungal activity than antibacterial activity. Additionally, compounds 2a with 1-methyltetrazole, 2c with benzothiazole and 2e with 6-chlorobenzothiazole moieties were found as the most active compounds.

scholarly journals The Burkholderia pseudomallei ΔasdMutant Exhibits Attenuated Intracellular Infectivity and Imparts Protection against Acute Inhalation Melioidosis in Mice

2011 ◽  
Vol 79 (10) ◽  
pp. 4010-4018 ◽  
Author(s):  
Michael H. Norris ◽  
Katie L. Propst ◽  
Yun Kang ◽  
Steven W. Dow ◽  
Herbert P. Schweizer ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Cell Model ◽  
Single Copy ◽  
Wild Type ◽  
Live Attenuated Vaccine ◽  
Content Type ◽  
Life Threatening ◽  
A Cell ◽  
Bioterrorism Agent

ABSTRACTBurkholderia pseudomallei, the cause of serious and life-threatening diseases in humans, is of national biodefense concern because of its potential use as a bioterrorism agent. This microbe is listed as a select agent by the CDC; therefore, development of vaccines is of significant importance. Here, we further investigated the growth characteristics of a recently createdB. pseudomallei1026b Δasdmutantin vitro, in a cell model, and in an animal model of infection. The mutant was typified by an inability to grow in the absence of exogenous diaminopimelate (DAP); upon single-copy complementation with a wild-type copy of theasdgene, growth was restored to wild-type levels. Further characterization of theB. pseudomalleiΔasdmutant revealed a marked decrease in RAW264.7 murine macrophage cytotoxicity compared to the wild type and the complemented Δasdmutant. RAW264.7 cells infected by the Δasdmutant did not exhibit signs of cytopathology or multinucleated giant cell (MNGC) formation, which were observed in wild-typeB. pseudomalleicell infections. The Δasdmutant was found to be avirulent in BALB/c mice, and mice vaccinated with the mutant were protected against acute inhalation melioidosis. Thus, theB. pseudomalleiΔasdmutant may be a promising live attenuated vaccine strain and a biosafe strain for consideration of exclusion from the select agent list.

scholarly journals Toxoflavin Produced byBurkholderia gladiolifromLycoris aureaIs a New Broad-Spectrum Fungicide

2019 ◽  
Vol 85 (9) ◽  
Author(s):  
Xiaodan Li ◽  
Yikui Li ◽  
Ren Wang ◽  
Qizhi Wang ◽  
Ling Lu
Keyword(s):  
Antifungal Activity ◽  
Broad Spectrum ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Endophytic Bacterium ◽  
Content Type ◽  
Burkholderia Gladioli ◽  
Lycoris Aurea ◽  
Resistant Mutants

ABSTRACTFungal infections not only cause extensive agricultural damage but also result in serious diseases in the immunodeficient populations of human beings. Moreover, the increasing emergence of drug resistance has led to a decrease in the efficacy of current antifungals. Thus, screening of new antifungal agents is imperative in the fight against antifungal drug resistance. In this study, we show that an endophytic bacterium,Burkholderia gladioliHDXY-02, isolated from the medicinal plantLycoris aurea, showed broad-spectrum antifungal activity against plant and human fungal pathogens. An antifungal ability assay indicated that the bioactive component was produced from strain HDXY-02 having an extracellular secreted component with a molecular weight lower than 1,000 Da. In addition, we found that this new antifungal could be produced effectively by liquid fermentation of HDXY-02. Furthermore, the purified component contributing to the antifungal activity was identified to be toxoflavin, a yellow compound possessing a pyrimido[5,4-e][1,2,4]triazine ring.In vitrobioactivity studies demonstrated that purified toxoflavin fromB. gladioliHDXY-02 cultures had a significant antifungal activity against the human fungal pathogenAspergillus fumigatus, resulting in abolished germination of conidia. More importantly, the growth inhibition by toxoflavin was observed in both wild-type and drug-resistant mutants (cyp51Aand non-cyp51A) ofA. fumigatus. Finally, an optimized protocol for the large-scale production of toxoflavin (1,533 mg/liter) has been developed. Taken together, our findings provide a promising biosynthetic resource for producing a new antifungal reagent, toxoflavin, from isolates of the endophytic bacteriumB. gladioli.IMPORTANCEHuman fungal infections are a growing problem associated with increased morbidity and mortality. Moreover, a growing number of antifungal-resistant fungal isolates have been reported over the past decade. Thus, the need for novel antifungal agents is imperative. In this study, we show that an endophytic bacterium,Burkholderia gladioli, isolated from the medicinal plantLycoris aurea, is able to abundantly secrete a compound, toxoflavin, which has a strong fungicidal activity not only against plant fungal pathogens but also against human fungal pathogensAspergillus fumigatusandCandida albicans,Cryptococcus neoformans, and the model filamentous fungusAspergillus nidulans. More importantly, toxoflavin also displays an efficacious inhibitory effect against azole antifungal-resistant mutants ofA. fumigatus. Consequently, our findings provide a promising approach to abundantly produce toxoflavin, which has novel broad-spectrum antifungal activity, especially against those currently problematic drug-resistant isolates.

scholarly journals Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Tatiana Y. Hargrove ◽  
Edward P. Garvey ◽  
William J. Hoekstra ◽  
Christopher M. Yates ◽  
Zdzislaw Wawrzak ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Aspergillus Fumigatus ◽  
Broad Spectrum ◽  
Fungal Infections ◽  
Enzymatic Reaction ◽  
Heme Iron ◽  
Antifungal Drugs ◽  
Drug Candidate ◽  
Investigational Drug ◽  
Content Type

ABSTRACT Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungus Aspergillus fumigatus. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole, ketoconazole, and posaconazole. The X-ray structure of the VT-1598/A. fumigatus CYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis of A. fumigatus CYP51/voriconazole and Candida albicans CYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using two A. fumigatus strains (strains 32820 and 1022) displayed a direct correlation between the effects of the drugs on CYP51B activity and fungal growth inhibition, indicating the noteworthy anti-A. fumigatus potency of VT-1598 and confirming its promise as a broad-spectrum antifungal agent.

scholarly journals In Vitro Confirmation of Siramesine as a Novel Antifungal Agent with In Silico Lead Proposals of Structurally Related Antifungals

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3504
Author(s):  
Josipa Vlainić ◽  
Ozren Jović ◽  
Ivan Kosalec ◽  
Oliver Vugrek ◽  
Rozelindra Čož-Rakovac ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agent ◽  
In Silico ◽  
Fungal Infections ◽  
Clinical Investigation ◽  
Fungal Resistance ◽  
Ergosterol Biosynthesis ◽  
Published Data ◽  
Slow Development

The limited number of medicinal products available to treat of fungal infections makes control of fungal pathogens problematic, especially since the number of fungal resistance incidents increases. Given the high costs and slow development of new antifungal treatment options, repurposing of already known compounds is one of the proposed strategies. The objective of this study was to perform in vitro experimental tests of already identified lead compounds in our previous in silico drug repurposing study, which had been conducted on the known Drugbank database using a seven-step procedure which includes machine learning and molecular docking. This study identifies siramesine as a novel antifungal agent. This novel indication was confirmed through in vitro testing using several yeast species and one mold. The results showed susceptibility of Candida species to siramesine with MIC at concentration 12.5 µg/mL, whereas other candidates had no antifungal activity. Siramesine was also effective against in vitro biofilm formation and already formed biofilm was reduced following 24 h treatment with a MBEC range of 50–62.5 µg/mL. Siramesine is involved in modulation of ergosterol biosynthesis in vitro, which indicates it is a potential target for its antifungal activity. This implicates the possibility of siramesine repurposing, especially since there are already published data about nontoxicity. Following our in vitro results, we provide additional in depth in silico analysis of siramesine and compounds structurally similar to siramesine, providing an extended lead set for further preclinical and clinical investigation, which is needed to clearly define molecular targets and to elucidate its in vivo effectiveness as well.

scholarly journals Berberine Antifungal Activity in Fluconazole-Resistant Pathogenic Yeasts: Action Mechanism Evaluated by Flow Cytometry and Biofilm Growth Inhibition in Candida spp.

2016 ◽  
Vol 60 (6) ◽  
pp. 3551-3557 ◽  
Author(s):  
Anderson Ramos da Silva ◽  
João Batista de Andrade Neto ◽  
Cecília Rocha da Silva ◽  
Rosana de Sousa Campos ◽  
Rose Anny Costa Silva ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Antifungal Activity ◽  
Cryptococcus Neoformans ◽  
Fungal Infections ◽  
Cell Activity ◽  
Candida Spp ◽  
Antifungal Effect ◽  
Content Type ◽  
Broth Microdilution Method ◽  
Fluconazole Resistant

The incidence of fungal infections and, in particular, the incidence of fungal antibiotic resistance, which is associated with biofilm formation, have significantly increased, contributing to morbidity and mortality. Thus, new therapeutic strategies need to be developed. In this context, natural products have emerged as a major source of possible antifungal agents. Berberine is a protoberberine-type isoquinoline alkaloid isolated from the roots, rhizomes, and stem bark of natural herbs, such asBerberis aquifolium,Berberis vulgaris,Berberis aristata, andHydrastis canadensis, and ofPhellodendron amurense. Berberine has been proven to have broad antibacterial and antifungal activity. In the present study, the potential antifungal effect of berberine against fluconazole-resistantCandidaandCryptococcus neoformansstrains, as well as against the biofilm form ofCandidaspp., was assessed. The antifungal effect of berberine was determined by a broth microdilution method (the M27-A3 method of the Clinical and Laboratory Standards Institute) and flow cytometry techniques, in which the probable mechanism of action of the compound was also assessed. For biofilm assessment, a colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine the susceptibility of sessile cells. The isolates used in the study belonged to the Laboratory of Bioprospection and Experiments in Yeast (LABEL) of the Federal University of Ceará. After 24 and 72 h, fluconazole-resistantCandidaandCryptococcus neoformansstrains showed berberine MICs equal to 8 μg/ml and 16 μg/ml, respectively. Cytometric analysis showed that treatment with berberine caused alterations to the integrity of the plasma and mitochondrial membranes and DNA damage, which led to cell death, probably by apoptosis. Assessment of biofilm-forming isolates after treatment showed statistically significant reductions in biofilm cell activity (P< 0.001).

scholarly journals Significantly Improved Pharmacokinetics Enhances In Vivo Efficacy of APX001 against Echinocandin- and Multidrug-Resistant Candida Isolates in a Mouse Model of Invasive Candidiasis

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Yanan Zhao ◽  
Min Hee Lee ◽  
Padmaja Paderu ◽  
Annie Lee ◽  
Cristina Jimenez-Ortigosa ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Standard Of Care ◽  
Multidrug Resistant ◽  
Once Daily ◽  
Content Type ◽  
Active Moiety ◽  
Life Threatening ◽  
Resistant Strains ◽  
Different Strains

ABSTRACT APX001 is a first-in-class, intravenous and orally available, broad-spectrum antifungal agent in clinical development for the treatment of life-threatening invasive fungal infections. The half-life of APX001A, the active moiety of APX001, is significantly shorter in mice than in humans (1.4 to 2.75 h in mice versus 2 to 2.5 days in humans), making the exploration of efficacy in mouse models difficult. After pretreatment with 1-aminobenzotriazole (ABT), a nonspecific cytochrome P450 inhibitor, greatly increased plasma APX001A exposure was observed in mice of different strains and of both genders. As a consequence, 26 mg/kg APX001 plus ABT sterilized kidneys in mice infected with Candida albicans, while APX001 alone at the same dose resulted in a modest burden reduction of only 0.2 log10 CFU/g, relative to the vehicle control. In the presence of ABT, 2 days of once-daily dosing with APX001 at 26 mg/kg also demonstrated significant in vivo efficacy in the treatment of Candida glabrata infections in mice. Potent kidney burden reduction was achieved in mice infected with susceptible, echinocandin-resistant, or multidrug-resistant strains. In contrast, the standard of care (micafungin) was ineffective in treating infections caused by the resistant C. glabrata isolates.

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