• Journal of Pharmacopuncture
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• v.27 no.2
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• pp.91-100
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• 2024

Objectives: Candida albicans is an opportunistic pathogen that occurs as harmless commensals in the intestine, urogenital tract, and skin. It has been influenced by a variety of host conditions and has now evolved as a resistant strain. The aim of this study was thus detect the fluconazole resistant C. albicans from the root caries specimens and to computationally evaluate the interactions of an opaque-phase ABC transporter protein with the Psidium guajava bio-active compounds. Methods: 20 carious scrapings were collected from patients with root caries and processed for the isolation of C. albicans and was screened for fluconazole resistance. Genomic DNA was extracted and molecular characterization of Cdrp1 and Cdrp2 was done by PCR amplification. P. guajava methanolic extract was checked for the antifungal efficacy against the resistant strain of C. albicans. Further in-silico docking involves retrieval of ABC transporter protein and ligand optimization, molinspiration assessment on drug likeness, docking simulations and visualizations. Results: 65% of the samples showed the presence of C.albicans and 2 strains were fluconazole resistant. Crude methanolic extract of P. guajava was found to be promising against the fluconazole resistant strains of C. albicans. In-silico docking analysis showed that Myricetin was a promising candidate with a high docking score and other drug ligand interaction scores. Conclusion: The current study emphasizes that bioactive compounds from Psidium guajava to be a promising candidate for treating candidiasis in fluconazole resistant strains of C. albicans However, further in-vivo studies have to be implemented for the experimental validation of the same in improving the oral health and hygiene.

• Mycobiology
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• v.31 no.2
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• pp.95-98
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• 2003

Aantifungal agents were tested against 30 clinical isolates of Cryptococcus neoformans var. neoformans using the NCCLS method(M27-A2). Posaconazole, itraconazole and amphotericin B had lower MIC than the remaining four antifungal agents. The MIC result for posaconazole was over 220-fold lower active than fluconazole. Fluconazole MICs for most isolates fell within the dose-dependant range. The overall MIC ranges and $MIC_{50}s$ were amphotericin B(0.03-0.25; 0.25), fluconazole(0.5-64; 16), itraconazole(0.015-1; 0.125), terbinafine(0.06->2; 1), caspofungin(8-32; 32), voriconazole(0.015-0.5; 0.25), and posaconazole(0.015-0.25; 0.06 ${\mu}g/ml$), respectively. In conclusion, the $MIC_{50}s$ of these drugs did not exhibit any sign of an upward shift with the exception of fluconazole and tendency cross-resistance between the seven drugs was not observed. We conclude that in vitro resistance to antifungal agents has not significantly changed despite the recent wide-spread use of triazoles for long-term treatment of Cryptococcal meningitis.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.2
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• pp.133-141
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• 2022

Candida is one of the most common causes of bloodstream infections and a leading cause of morbidity and mortality among hospitalized patients. The purpose of this study was to provide important information for formulating empirical treatment plans for candidemia by investigating the antifungal resistance rate of Candida. Among the Candida strains (973 cases) isolated from blood culture tests at the S hospital in 2009~2018, 4.7% (N=44) comprising the Candida spp. (932 strains) showed resistance to fluconazole. The resistant strains included C. albicans, C. parapsilosis, C. tropicalis, and C. glabrata. In addition Candida spp. (947 strains) showed resistance to amphotericin B (N=6, 0.6%), flucytosine (N=23, 2.4%) and voriconazole (N=24, 3.1%). C. albicans was resistant to fluconazole (N=23, 6.9%) and voriconazole (N=21, 6.0%), The statistical analysis showed that C. albicans and non-albicans Candida species were resistant to fluconazole (P=0.039) and voriconazole (P<0.001). A monitoring system to understand the rate of candidiasis infections in a hospital setting is required. It is also important to make the right choice of the antifungal agent based on drug susceptibility patterns. Therefore, an infection surveillance policy that tracks Candida resistance through regular antifungal susceptibility tests is necessary.

• Journal of Microbiology and Biotechnology
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• v.31 no.5
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• pp.659-666
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• 2021

After Candida albicans, Candida glabrata is one of the most common fungal species associated with candidemia in nosocomial infections. Rapid acquisition of nutrients from the host is important for the survival of pathogens which possess the metabolic flexibility to assimilate different carbon and nitrogen compounds. In Saccharomyces cerevisiae, nitrogen assimilation is controlled through a mechanism known as Nitrogen Catabolite Repression (NCR). NCR is coordinated by the action of four GATA factors; two positive regulators, Gat1 and Gln3, and two negative regulators, Gzf3 and Dal80. A mechanism in C. glabrata similar to NCR in S. cerevisiae has not been broadly studied. We previously showed that in C. glabrata, Gln3, and not Gat1, has a major role in nitrogen assimilation as opposed to what has been observed in S. cerevisiae in which both factors regulate NCR-sensitive genes. Here, we expand the knowledge about the role of Gln3 from C. glabrata through the transcriptional analysis of BG14 and gln3Δ strains. Approximately, 53.5% of the detected genes were differentially expressed (DEG). From these DEG, amino acid metabolism and ABC transporters were two of the most enriched KEGG categories in our analysis (Up-DEG and Down-DEG, respectively). Furthermore, a positive role of Gln3 in AAA assimilation was described, as was its role in the transcriptional regulation of ARO8. Finally, an unexpected negative role of Gln3 in the gene regulation of ABC transporters CDR1 and CDR2 and its associated transcriptional regulator PDR1 was found. This observation was confirmed by a decreased susceptibility of the gln3Δ strain to fluconazole.

• YAKHAK HOEJI
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• v.59 no.6
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• pp.259-265
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• 2015

In recent, there are increasing reports about pharmacological activities of Crataegi Fructus which has been used for many centuries as medicinal and food sources in East Asia. However, its antifungal efficacy needs to be investigated. Thus, in the current study, we determined synergistic antifungal activity of the Crataegi Fructus extract (CFE) when combined with fluconazole (FLC) against disseminated candidiasis due to Candida albicans. This fungus is one of the most problematic fungal pathogens. Data resulting from a microdilution susceptibility test showed that CFE had a dose-dependent antifungal activity. When the extract was combined with FLC, the activity was synergistic. For example, the antifungal activity by the combination of CFE at $20{\mu}g/ml$ plus FLC at $0.1{\mu}g/ml$ was 4 times more effective than antifungal activity by FLC alone at the same concentration (P<0.05). In the murine model of disseminated candidiasis, the combination therapy potentiated resistance of mice, resulting in 80% of C. albicans-infected animals surviving the entire period of 40 days observation, whereas mice given CFE alone or FLC alone all died with 17 and 23 days, respectively, although they survived longer than the untreated control animals (P<0.05). The CFE's antifungal activity seemed to be related to the blockage of hyphal production of C. albicans yeast cells. In summary, CFE has a synergistic antifungal activity, which can be produced by combining CFE with FLC. Thus, our data strongly indicate that CFE may be a potential candidate as an antifungal agent for combination therapy.

• Fisheries and Aquatic Sciences
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• v.17 no.2
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• pp.209-214
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• 2014

With the continuing demand for new solutions in the development of effective and safe candidiasis therapies, we investigated the efficacy of an antifungal agent from the marine brown alga Eisenia bicyclis. The methanolic extract of E. bicyclis evinced potential antifungal activity against Candida species. The ethyl acetate (EtOAc)-soluble extract from E. bicyclis demonstrated the strongest antifungal activity against Candida species among five solvent-soluble extracts. Indeed, the EtOAc-soluble extract showed minimum inhibitory concentrations (MICs) ranging from 4 to 8 mg/mL. Furthermore, the EtOAc-soluble extract considerably reversed high-level fluconazole resistance of Candida species. The MIC values of fluconazole against Candida species decreased substantially (from 64 to $4{\mu}g/mL$) in combination with the MIC of the EtOAc-soluble extract (4 mg/mL). The fractional inhibitory concentration indices of fluconazole ranged from 0.531 to 0.625 in combination with 4, 2, or 1 mg/mL of the EtOAc-soluble extract against Candida isolates, indicating that these combinations exert a marked synergistic effect against Candida isolates. These findings imply that compounds derived from E. bicyclis can be a potential source of natural antifungal agents against Candida species.

• Journal of Microbiology and Biotechnology
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• v.27 no.4
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• pp.685-693
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• 2017

Candidiasis involving the biofilms of Candida albicans is a threat to immunocompromised patients. Candida biofilms are intrinsically resistant to the antifungal drugs and hence novel treatment strategies are desired. The study intended to evaluate the anti-Candida activity of allyl isothiocyanate (AITC) alone and with fluconazole (FLC), particularly against the biofilms. Results revealed the concentration-dependent activity of AITC against the planktonic growth and virulence factors of C. albicans. Significant (p <0.05) inhibition of the biofilms was evident at ${\leq}1mg/ml$ concentrations of AITC. Notably, a combination of 0.004 mg/ml of FLC and 0.125 mg/ml of AITC prevented the biofilm formation. Similarly, the preformed biofilms were significantly (p <0.05) inhibited by the AITC-FLC combination. The fractional inhibitory concentration indices ranging from 0.132 to 0.312 indicated the synergistic activity of AITC and FLC against the biofilm formation and the preformed biofilms. No hemolytic activity at the biofilm inhibitory concentrations of AITC and the AITC-FLC combination suggested the absence of cytotoxic effects. The recognizable synergy between AITC and FLC offers a potential therapeutic strategy against biofilm-associated Candida infections.

• Biomedical Science Letters
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• v.30 no.2
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• pp.73-80
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• 2024

The aim of this study was to investigate the distribution and antifungal susceptibilities of Candida spp. from blood culture to provide useful information on empirical treatment of Candidemia. We investigated distribution and antifungal susceptibilities of Candida spp. isolated from blood culture during an 8-years (2016-2023) in a C-University hospital. Over 8 years, 1,182 Candida strains from blood culture were isolated, which was fourth most common cause of bloodstream infection. Among nonduplicated 350 Candida strains, C. albicans was the most common with 45.43%, followed by C. glabrata (17.43%), C. tropicalis (17.43%), C. parapsilosis (14.86%), C. guilliermondii (1.71%), C. krusei (0.86%), C. lusitaniae (0.86%), C. ciferrii (0.57%). In the antifungal susceptibility testing on 323 Candida strains, the non-susceptibility rate was 2.48% for amphotericin B, 1,71% for flucytosine, 3.09% for fluconazole, 4.66% for voriconazole, 5.57% for caspofungin, and 0.62% for micafungin. In particular, C. albicans showed non-susceptibility of 8.23% to voriconazole, and C. glabrata showed 14.81% and 24.59% to fluconazole and caspofungin, respectively. These data showed that the prevalence of candidemia is very common, and antifungal resistance in Candida spp., especially C. glabrata, is increasing. Therefore, periodic surveillance of prevalence and antifungal susceptibility of blood culture is very important for clinical laboratory.

• Mycobiology
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• v.46 no.2
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• pp.114-121
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• 2018

Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen, Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and endoplasmic reticulum stress. However, the mon1 deletion mutant showed more resistance to the antifungal agent fluconazole. In vivo studies demonstrated that compared to the wild-type strain, the mon1 deletion mutant attenuated virulence in the Galleria mellonella insect model. Moreover, the mon1 deletion mutant was avirulent in the murine inhalation model. These results demonstrate that Mon1 plays a crucial role in stress survival and pathogenicity in C. neoformans.

• YAKHAK HOEJI
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• v.55 no.3
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• pp.234-239
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• 2011

Glycycoumarin, a 3-arylcoumarine isolated from Glycyrrhizae radix (a family of Leguminosae), is reported to have anti-bacterial activity. However, its antifungal activity is still unknown. In this present study, the antifungal activity of glycycoumarin (GLM) against Candida albicans, a polymorphic fungus was investigated. Possible mechanism such as blocking of the hyphal induction was also analyzed. By the in-vitro susceptibility analysis, GLM showed anticandidal activity, resulting in an almost complete inhibition of the fungal growth at a concentration of 320 ${\mu}g/ml$, which was equivalent to the efficacy of fluconazole at the same dose. In the murine model of disseminated candidiasis GLM enhanced resistance of mice against the disseminated disease (P<0.05), resulting in 60% protection of GLM-treated mice group during a period of 21-day observation. As for its mechanism of the antifungal activity, GLM blocked hyphal production, one of the important of virulence factors by the fungus, from the yeast form of C. albicans (P<0.01). These data indicate that GLM may contribute to the perspectives that focus on the development of a novel agent with antifungal activity specific for C. albicans infection.