Ent‐ hardwickiic acid from C. pubiflora and its microbial metabolites are more potent than fluconazole in vitro against Candida glabrata

2022 ◽  
Author(s):  
M.V.S. Teixeira ◽  
L.M. Fernandes ◽  
V.S. de Paula ◽  
A.G. Ferreira ◽  
N.A.J.C. Furtado
Keyword(s):  
Candida Glabrata ◽  
Microbial Metabolites

The role of aromatic microbial metabolites

2018 ◽  
pp. 97-108
Author(s):  
Н.В. Белобородова ◽  
В.В. Мороз ◽  
А.Ю. Бедова
Keyword(s):  
Process Integration ◽  
Biological Effects ◽  
Clinical Findings ◽  
Multiple Organ ◽  
Critical Conditions ◽  
Clear Understanding ◽  
Microbial Metabolites ◽  
Blood Concentrations

Интеграция метаболизма макроорганизма и его микробиоты, обеспечивающая в норме симбиоз и саногенез, нарушается при заболеваниях, травме, критическом состоянии, и вектор взаимодействия может изменяться в пользу прокариотов по принципу «метаболиты бактерий - против хозяина». Анализ литературы показал, что, с одной стороны, имеется живой интерес к ароматическим микробным метаболитам, с другой - отсутствует четкое представление об их роли в организме человека. Публикации, касающиеся ряда ароматических микробных метаболитов (фенилкарбоновых кислот, ФКК), как правило, не связаны между собой по тематике и направлены на решение тех или иных прикладных задач в разных областях биологии и медицины. Цель обзора - анализ информации о происхождении, биологических эффектах ФКК в экспериментах in vitro и in vivo , и клинических наблюдениях. Обобщая результаты приведенных в обзоре исследований на клеточном, субклеточном и молекулярном уровнях, логично предположить участие ароматических микробных метаболитов в патогенезе полиорганной недостаточности при сепсисе. Наиболее перспективным для раскрытия роли ароматических микробных метаболитов представляется изучение механизмов вторичной почечной недостаточности и септической энцефалопатии. Важным направлением для будущих исследований является изучение влияния продуктов микробной биодеградации ароматических соединений на развитие диссеминированного внутрисосудистого свертывания крови, артериальной гипотензии и септического шока. Результаты дальнейших исследований будут иметь не только фундаментальное значение, но и обогатят практическую медицину новыми диагностическими и лечебными технологиями. Significant increases in blood concentrations of some aromatic metabolites (phenylcarboxylic acids, PhCAs) in patients with sepsis have been previously shown. Enhanced bacterial biodegradation of aromatic compounds has been demonstrated to considerably contribute to this process. Integration of macroorganism metabolism and its microbiota, which provides normal symbiosis and sanogenesis, is disturbed in diseases, trauma, and critical conditions. Direction of this interaction may change in favor of prokaryotes according to the principle, “bacterial metabolites are against the host”. Analysis of literature showed a particular interest of many investigators to aromatic microbial metabolites. However, there is no clear understanding of their role in the human body. Publications on PhCAs are generally not thematically interrelated and usually focus on solving applied tasks in different fields of biology and medicine. The aim of this work was to consolidate existing information about origin and biological effects of PhCAs in in vitro / in vivo experiments and some clinical findings. The presented summary of reported data from studies performed at cellular, sub-cellular, and molecular levels suggests participation of aromatic microbial metabolites in the pathogenesis of multiple organ failure in sepsis. Studying mechanisms of secondary renal failure and septic encephalopathy is most promising for discovering the function of aromatic microbial metabolites. Effects of microbial biodegradation products of aromatic substances on development of disseminated intravascular coagulation, hypotension, and septic shock are an important challenge for future studies. Results of further investigations will be not only fundamental, but will also enrich medical practice with new diagnostic and therapeutic technologies.

scholarly journals In Vitro Activity of Ibrexafungerp, a Novel Glucan Synthase Inhibitor against Candida glabrata Isolates with FKS Mutations

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Natalie S. Nunnally ◽  
Kizee A. Etienne ◽  
David Angulo ◽  
Shawn R. Lockhart ◽  
Elizabeth L. Berkow
Keyword(s):  
Candida Glabrata ◽  
Vitro Activity ◽  
Good Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Glucan Synthase ◽  
Content Type ◽  
Synthase Inhibitor

ABSTRACT Ibrexafungerp is a first-in-class glucan synthase inhibitor. In vitro activity was determined for 89 Candida glabrata isolates with molecularly identified FKS1 or FKS2 mutations conferring resistance to the echinocandins. All isolates were resistant to at least one echinocandin (i.e., anidulafungin, caspofungin, or micafungin) by broth microdilution. Results for ibrexafungerp were compared with those for each echinocandin. Ibrexafungerp had good activity against all echinocandin-resistant C. glabrata isolates.

scholarly journals Microbial Metabolites of Flavanols in Urine are Associated with Enhanced Anti-Proliferative Activity in Bladder Cancer Cells In Vitro

2021 ◽  
pp. 1-17
Author(s):  
Laura E. Griffin ◽  
Sarah E. Kohrt ◽  
Atul Rathore ◽  
Colin D. Kay ◽  
Magdalena M. Grabowska ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Proliferative Activity ◽  
Microbial Metabolites ◽  
Bladder Cancer Cells

scholarly journals Discovery of a Novel Class of Orally Active Antifungal β-1,3-d-Glucan Synthase Inhibitors

2011 ◽  
Vol 55 (11) ◽  
pp. 5099-5106 ◽  
Author(s):  
Scott S. Walker ◽  
Yiming Xu ◽  
Ilias Triantafyllou ◽  
Michelle F. Waldman ◽  
Cara Mendrick ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Glabrata ◽  
Pharmacokinetic Data ◽  
Morphological Response ◽  
Glucan Synthase ◽  
Content Type ◽  
Safety Issues ◽  
Spontaneous Mutants ◽  
Orally Active

ABSTRACTThe echinocandins are a class of semisynthetic natural products that target β-1,3-glucan synthase (GS). Their proven clinical efficacy combined with minimal safety issues has made the echinocandins an important asset in the management of fungal infection in a variety of patient populations. However, the echinocandins are delivered only parenterally. A screen for antifungal bioactivities combined with mechanism-of-action studies identified a class of piperazinyl-pyridazinones that target GS. The compounds exhibitedin vitroactivity comparable, and in some cases superior, to that of the echinocandins. The compounds inhibit GSin vitro, and there was a strong correlation between enzyme inhibition andin vitroantifungal activity. In addition, like the echinocandins, the compounds caused a leakage of cytoplasmic contents from yeast and produced a morphological response in molds characteristic of GS inhibitors. Spontaneous mutants ofSaccharomyces cerevisiaewith reduced susceptibility to the piperazinyl-pyridazinones had substitutions inFKS1. The sites of these substitutions were distinct from those conferring resistance to echinocandins; likewise, echinocandin-resistant isolates remained susceptible to the test compounds. Finally, we present efficacy and pharmacokinetic data on an example of the piperazinyl-pyridazinone compounds that demonstrated efficacy in a murine model ofCandida glabratainfection.

scholarly journals In Vitro Activities of Voriconazole in Combination with Three Other Antifungal Agents against Candida glabrata

2004 ◽  
Vol 48 (9) ◽  
pp. 3317-3322 ◽  
Author(s):  
Francesco Barchiesi ◽  
Elisabetta Spreghini ◽  
Monia Maracci ◽  
Annette W. Fothergill ◽  
Isabella Baldassarri ◽  
...  
Keyword(s):  
Candida Glabrata ◽  
Antifungal Agents ◽  
Beneficial Effects ◽  
Synergistic Interactions ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Disk Diffusion Assay ◽  
Combination Regimens

ABSTRACT Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to ≤1.0 μg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was ≥2.0 μg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.

scholarly journals Antifungal Activity of SCY-078 and Standard Antifungal Agents against 178 Clinical Isolates of Resistant and Susceptible Candida Species

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Wiley A. Schell ◽  
A. M. Jones ◽  
Katyna Borroto-Esoda ◽  
Barbara D. Alexander
Keyword(s):  
Candida Glabrata ◽  
Antifungal Agents ◽  
Candida Parapsilosis ◽  
Candida Krusei ◽  
Wild Type ◽  
Content Type ◽  
Clinical Resistance ◽  
Excellent Activity ◽  
Candida Lusitaniae

ABSTRACT SCY-078 in vitro activity was determined for 178 isolates of resistant or susceptible Candida albicans, Candida dubliniensis, Candida glabrata, Candida krusei, Candida lusitaniae, and Candida parapsilosis, including 44 Candida isolates with known genotypic (FKS1 or FKS2 mutations), phenotypic, or clinical resistance to echinocandins. Results were compared to those for anidulafungin, caspofungin, micafungin, fluconazole, and voriconazole. SCY-078 was shown to have excellent activity against both wild-type isolates and echinocandin- and azole-resistant isolates of Candida species.

scholarly journals Green tea phytocompounds targets Lansterol 14-α demethylase against ergosterol biosynthesis in Candida glabrata

2021 ◽  
Vol 12 (3) ◽  
pp. 1793-1797
Author(s):  
Priyanka Sirari ◽  
Jigisha Anand ◽  
Devvret ◽  
Ashish Thapliyal ◽  
Nishant Rai
Keyword(s):  
Green Tea ◽  
Candida Glabrata ◽  
Scientific Evidence ◽  
Epigallocatechin Gallate ◽  
Ergosterol Biosynthesis ◽  
Epicatechin Gallate ◽  
P450 Monooxygenase ◽  
Antifungal Potential ◽  
Inhibitory Potential

Green tea is credited as one of the world’s healthiest drinks with enriched antioxidants. It is known for its multi-beneficial health benefits against diabetes, blood pressure, hypertension, gastro-intestinal upset and is bestowed with significant antimicrobial potential. There are previous scientific evidence highlighting the antifungal potential of green tea and has identified it as a potential inhibitor of non-albicans Candida species. Lansterol 14-α demethylase (Erg 11) or CYP51 protein belongs to the cytochrome P450 monooxygenase (CYP) superfamily. Erg 11 is involved in ergosterol biosynthesis and has a significant role in azole drug resistance in Candida glabrata. The present study attempted to identify the inhibitory potential of green tea phytocompounds against inhibition of Erg 11 in Candida glabrata using bioinformatics tool viz., autodock vina software. Out of 15 green tea phytocompounds investigated, the study identified, Rutin (-10.5 kcal) Kaempferitrin (-9.4kcal), Epigallocatechin gallate (-10kcal), Epicatechin gallate (-8.7kcal), and Coumaroylquinic acid (-8.6kcal) acid as the potent phytocompounds which showed significant molecular interaction with Erg 11 in Candida glabrata. In attribution to the constant emergence of azole-resistant isolates, this preliminary analysis therefore, indicated the potential of green tea phytocompounds against inhibition of non-albicans Candida specific candidiasis. However, further, in vitro antimicrobial efficacy of these phytocompounds, the dose regime, drug likeliness, and cytotoxic analysis are required to be investigated and validated.

scholarly journals Synthesis, Characterization and in Vitro Antifungal Effect of Some Butyltin(IV) N-substituted 2-aminoethanethiolates

2001 ◽  
Vol 8 (3) ◽  
pp. 165-169 ◽  
Author(s):  
A. Smicka ◽  
V. Buchta ◽  
K. Handlir
Keyword(s):  
Candida Glabrata ◽  
Pathogenic Fungi ◽  
Trichophyton Mentagrophytes ◽  
Candida Krusei ◽  
Antifungal Drugs ◽  
Antifungal Effect ◽  
Absidia Corymbifera ◽  
Structure Activity ◽  
Trichosporon Beigelii

Six new N-substituted di- and tributyltin 2-aminoethanethiolates (cysteaminates) have been prepared and characterised by H1, C13 and S119n NMR spectroscopy. All these compounds exhibit a good in vitro antifungal effect against selected types of human pathogenic fungi (Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata, Trichosporon beigelii, Aspergillus fumigatus, Absidia corymbifera, Trichophyton mentagrophytes) and their activity is comparable with that of some antifungal drugs commonly used in the clinical use like ketoconazole. The structure-activity relationships in these compounds are discussed.

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