Role of Candida glabrata as nosocomial pathogen and its susceptibility to Fluconazole, Voriconazole, Caspofungin, Micafungin and Amphotericin B

Candida has different types that could cause bloodstream infections. A total number of 150 samples were collected from candidemia patients and examined. The Candida spp. Species isolated from blood samples were analysed. These were identified by culturing the species using different media, namely the chromogenic agar test. Then, the virulence factors of all samples were tested. The Candida glabrata isolates were tested with six commercial antifungal drugs. C. glabrata 67 (44.6%), C. albicans 34 (22.6%), C. krusei 18 (12%), C. tropicalis 17 (11.3%), and C. parasilosis 14 (9.3%). the production of phospholipase ranged between 0.63-0.99 mm. It was found that 96% of the species showed phospholipase activity in aerobic conditions. The protease activities of Candida spp. Isolates were experimentally tested by area of inhibition around the colonies, where 59.3% had the double (++) protease activity, 31.4% with (+) grade, and 9.3% had (–) grade or clear zone around the colony. The hemolytic capacity ranged from 0.69-0.89 in the optimum aerobic environments. Finally, 38.33% of the isolated Candida spp. were positive and 61.67% negative for biofilm formation. Out of the total positive Candida spp. for biofilm formation, 21.73% were strong biofilm producers, and 78.27% were weak. Minimum fungicidal concentration (MFC) of Fluconazole for C. glabrata isolates was not appropriate (NA) due to the occurrence of low inhibition tested for species. Micafungin exhibited the lowest fungicidal activity against C. glabrata ranging from 0.03 - 0.125, while Fluconazole showed the highest.

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Evaluation of the Effectiveness of Crotoxin as an Antiseptic against Candida spp. Biofilms

Toxins ◽

10.3390/toxins12090532 ◽

2020 ◽

Vol 12 (9) ◽

pp. 532

Author(s):

Amanda Pissinatti Canelli ◽

Taís Fernanda dos Santos Rodrigues ◽

Vivian Fernandes Furletti de Goes ◽

Guilherme Ferreira Caetano ◽

Maurício Ventura Mazzi

Keyword(s):

Biofilm Formation ◽

Colorimetric Assay ◽

Oral Candidiasis ◽

Hacat Cells ◽

Candida Spp ◽

Oral Infections ◽

Minimum Fungicidal Concentration ◽

Antimicrobial Susceptibility Tests ◽

Susceptibility Tests

The growing number of oral infections caused by the Candida species are becoming harder to treat as the commonly used antibiotics become less effective. This drawback has led to the search for alternative strategies of treatment, which include the use of antifungal molecules derived from natural products. Herein, crotoxin (CTX), the main toxin of Crotalus durissus terrificus venom, was challenged against Candida tropicalis (CBS94) and Candida dubliniensis (CBS7987) strains by in vitro antimicrobial susceptibility tests. Minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and inhibition of biofilm formation were evaluated after CTX treatment. In addition, CTX-induced cytotoxicity in HaCaT cells was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) colorimetric assay. Native CTX showed a higher antimicrobial activity (MIC = 47 μg/mL) when compared to CTX-containing mouthwash (MIC = 750 μg/mL) and nystatin (MIC = 375 μg/mL). Candida spp biofilm formation was more sensitive to both CTX and CTX-containing mouthwash (IC100 = 12 μg/mL) when compared to nystatin (IC100 > 47 μg/mL). Moreover, significant membrane permeabilization at concentrations of 1.5 and 47 µg/mL was observed. Native CTX was less cytotoxic to HaCaT cells than CTX-containing mouthwash or nystatin between 24 and 48 h. These preliminary findings highlight the potential use of CTX in the treatment of oral candidiasis caused by resistant strains.

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The role of chelators in preventing biofilm formation and catheter-related bloodstream infections

Current Opinion in Infectious Diseases ◽

10.1097/qco.0b013e32830634d8 ◽

2008 ◽

Vol 21 (4) ◽

pp. 385-392 ◽

Cited By ~ 73

Author(s):

Issam I Raad ◽

Xiang Fang ◽

Xavier M Keutgen ◽

Ying Jiang ◽

Robert Sherertz ◽

...

Keyword(s):

Biofilm Formation ◽

Bloodstream Infections

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Emergence of Azole Resistant Candida Glabrata as an Important Cause of Hospital Acquired Infection: Its Risk Factors and Impact

Asploro Journal of Biomedical and Clinical Case Reports ◽

10.36502/2020/asjbccr.6202 ◽

2020 ◽

Vol 3 (2) ◽

pp. 141-146

Author(s):

Sarkar T

Keyword(s):

Candida Glabrata ◽

Acquired Resistance ◽

Human Microbiome ◽

Bloodstream Infections ◽

Candida Spp ◽

Mortality And Morbidity ◽

Hospital Acquired Infection ◽

The Usa ◽

Proportional Increase ◽

Hospital Acquired

Candida spp. colonizes the human host and coexists with members of the human microbiome. Candida glabrata are aggressive pathogens, have many virulence factors that lead to serious recurrent candidiasis. Their ability to form a complex biofilm, inability to form hyphae, and inability to secrete hydrolase lead to antifungal resistance. Candidemia is the fourth most common bloodstream infection [1]. Candidemia remains a major source of mortality and morbidity. Mortality among patients with invasive candidiasis is as high as 40%, even when patients receive antifungal therapy [2]. More than 90% of invasive diseases are caused by the 5 most common Candida spp. C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei [3]. The distribution of Candida species has been changing over the last decade, with a decrease in the proportion of C. albicans and an increase in C. glabrata and C. parapsilosis. More than 50% of bloodstream infections are caused by non-albicans Candida [2,4]. The largest proportional increase in the USA is in C. glabrata, which accounts for one third or more of all candidemia isolates [5-7]. C.glabrata are associated with high mortality. Candida glabrata develop acquired resistance following exposure to antifungal agents [8]. 50% of C. glabrata are resistant to fluconazole [9,10]. Furthermore, 9% of C. glabrata that are resistant to fluconazole are also resistant to the echinocandins [8,11].

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Loss-of-function ROX1 mutations suppress the fluconazole susceptibility of upc2AΔ mutation in Candida glabrata, implicating additional positive regulators of ergosterol biosynthesis

10.1101/2021.10.07.463606 ◽

2021 ◽

Author(s):

Tomye L Ollinger ◽

Bao Vu ◽

Daniel Murante ◽

Josie Parker ◽

Lucia Simonicova ◽

...

Keyword(s):

Candida Glabrata ◽

Genetic Interaction ◽

Pathogenic Fungi ◽

Antifungal Drugs ◽

Negative Regulator ◽

Ergosterol Biosynthesis ◽

Loss Of Function ◽

Candida Spp ◽

Ergosterol Biosynthesis Inhibitors ◽

Positive Regulators

Two of the major classes of antifungal drugs in clinical use target ergosterol biosynthesis. Despite its importance, our understanding of the transcriptional regulation of ergosterol biosynthesis genes in pathogenic fungi is essentially limited to the role of hypoxia and sterol-stress induced transcription factors such as Upc2 and Upc2A as well as homologs of Sterol Response Element Binding (SREB) factors. To identify additional regulators of ergosterol biosynthesis in Candida glabrata, an important human fungal pathogen with reduced susceptibility to ergosterol biosynthesis inhibitors relative to other Candida spp., we used a serial passaging strategy to isolate suppressors of the fluconazole hypersusceptibility of a upc2AΔ deletion mutant. This led to the identification of loss of function mutants in two genes: ROX1, the homolog of a hypoxia gene transcriptional suppressor in Saccharomyces cerevisiae, and CST6, a transcription factor that is involved in the regulation of carbon dioxide response in C. glabrata. Here, we describe a detailed analysis of the genetic interaction of ROX1 and UPC2A. In the presence of fluconazole, loss of Rox1 function restores ERG11 expression to the upc2AΔ mutant and inhibits the expression of ERG3 and ERG6, leading to increased levels or ergosterol and decreased levels of the toxic sterol, 14α methyl-ergosta-8,24(28)-dien-3β, 6α-diol, relative to upc2AΔ. Our observations establish that Rox1 is a negative regulator of ERG gene biosynthesis and indicate that a least one additional positive transcriptional regulator of ERG gene biosynthesis must be present in C. glabrata.

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Surveillance and characterization of Candida bloodstream infections in a Serbian tertiary care hospital

The Journal of Infection in Developing Countries ◽

10.3855/jidc.7970 ◽

2016 ◽

Vol 10 (06) ◽

pp. 643-656 ◽

Cited By ~ 10

Author(s):

Predrag Stojanovic ◽

Nikola Stojanovic ◽

Zorica Stojanovic-Radic ◽

Valentina Arsić Arsenijević ◽

Suzana Otasevic ◽

...

Keyword(s):

Tertiary Care Hospital ◽

Antifungal Susceptibility ◽

Tertiary Care ◽

Bloodstream Infections ◽

Drug Susceptibility ◽

Antifungal Drugs ◽

Care Hospital ◽

Candida Spp ◽

Multivariate Statistical ◽

Medical Histories

Introduction: Candida spp. frequently cause hospital-acquired bloodstream infections (BSI) with a high mortality rate (up to 70%). We analyzed the frequency, infection characteristics, potential predisposing factors, susceptibility to antifungal drugs, biofilm production and other virulence characteristics of Candida spp. isolates obtained from a tertiary care hospital in Niš, Serbia, during a one year period. Methods: Medical histories, characteristics of isolated strains and drug susceptibility, as well as the effect on the function of isolated macrophages and other virulence features were evaluated. The obtained results were subjected to student’s t-test and multivariate statistical analyzes. Results: Herein we report an annual incidence of 3.65 cases of C. albicans, C. lusitaniae and C. lipolytica infections per 105 population. Out of eight isolated strains, two (25%) were shown to be strong biofilm producers, one (12.5%) caused hemolysis on blood agar and in two (25%) cases macrophages were able to completely eliminate the yeast colonies. Chronic kidney disease, diabetes, malignant and other diseases were present in 37.5, 62.5, 50 and 75%, respectively, in the study group. All patients with Candida BSI received antifungal therapy (amphotericin B), however, hospital mortality was observed in 25% of patients. Conclusions: Evaluation of local Candida epidemiology, antifungal susceptibility and virulence factors, as well as personalized patient risk factors are important for the surveillance of Candida BSI, especially in intensive care unit patients and may contribute to the improved options and outcome for patients with Candida BSI.

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Inhibitory Effect of (-)-myrtenol alone and in combination with antifungal agents on Candida spp.

Research Society and Development ◽

10.33448/rsd-v10i15.22434 ◽

2021 ◽

Vol 10 (15) ◽

pp. e35101522434

Author(s):

Bruno Bezerra Cavalcanti ◽

Hermes Diniz Neto ◽

Walicyranison Plinio da Silva-Rocha ◽

Edeltrudes de Oliveira Lima ◽

José Maria Barbosa Filho ◽

...

Keyword(s):

Minimum Inhibitory Concentration ◽

Antifungal Agent ◽

Antifungal Agents ◽

Inhibitory Concentration ◽

Inhibitory Effect ◽

Antifungal Drugs ◽

Additive Effects ◽

Candida Spp ◽

Minimum Fungicidal Concentration ◽

Fungicide Activity

The aim of this study was to examine the effects of (-)-myrtenol alone and combined with antifungal agents against Candida spp. The Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration of (-)-myrtenol and fluconazole against C. albicans and C. parapsilosis strains was obtained using CLSI guidelines. Combination of (-)-myrtenol with antifungal drugs was determined by checkboard test. The (-) myrtenol showed MIC ranging from 256 to 512 µg/mL against both species assay. And the MFC was 512 µg/mL, demonstrated nature fungicidal (MFC/MIC < 4). In addition, combination of antifungal agents (amphotericin B and fluconazole) and (-) myrtenol showed synergistic and additive effects on strains assays. Based on these results, the present study demonstrates that (-) myrtenol showed strong fungicide activity against Candida spp. In addition, Combination of antifungal agents and (-) myrtenol reduces the effective concentrations of both the agents with synergistic to additive effects. Therefore, (-) myrtenol has potential to be developed into an antifungal agent.

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Role of purified beta-glucanase from lactobacillus acidophilus in disruption of biofilm formation by candida spp. causing of denture stomatitis

Materials Today Proceedings ◽

10.1016/j.matpr.2021.12.021 ◽

2021 ◽

Author(s):

Jawaher M. Taher ◽

Noor Natik Raheem

Keyword(s):

Lactobacillus Acidophilus ◽

Biofilm Formation ◽

Candida Spp ◽

Denture Stomatitis ◽

Beta Glucanase

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In Vitro Activity of Carbosilane Cationic Dendritic Molecules on Prevention and Treatment of Candida Albicans Biofilms

Pharmaceutics ◽

10.3390/pharmaceutics12100918 ◽

2020 ◽

Vol 12 (10) ◽

pp. 918

Author(s):

Irene Heredero-Bermejo ◽

Natalia Gómez-Casanova ◽

Sara Quintana ◽

Juan Soliveri ◽

Francisco Javier de la Mata ◽

...

Keyword(s):

Cell Viability ◽

Biofilm Formation ◽

Fungal Pathogens ◽

Resistance Mechanisms ◽

Antifungal Drugs ◽

Vitro Activity ◽

In Vitro Activity ◽

Candida Spp ◽

Screening Process

Candida spp. are one of the most common fungal pathogens. Biofilms formed by Candidaalbicans offer resistance mechanisms against most antifungal agents. Therefore, development of new molecules effective against these microorganisms, alone or in combination with antifungal drugs, is extremely necessary. In the present work, we carried out a screening process of different cationic carbosilane dendritic molecules against C. albicans. In vitro activity against biofilm formation and biofilms was tested in both Colección Española de Cultivos Tipo (CECT) 1002 and clinical C. albicans strains. Cytotoxicity was studied in human cell lines, and biofilm alterations were observed by scanning electron microscopy (SEM). Antifungal activity of the carbosilane dendritic molecules was assessed by monitoring cell viability using both established and novel cell viability assays. One out of 14 dendritic molecules tested, named BDSQ024, showed the highest activity with a minimum biofilm inhibitory concentration (MBIC) for biofilm formation and a minimum biofilm damaging concentration (MBDC) for existing biofilm of 16–32 and 16 mg/L, respectively. Synergy with amphotericin (AmB) and caspofungin (CSF) at non-cytotoxic concentrations was found. Therefore, dendritic compounds are exciting new antifungals effective at preventing Candida biofilm formation and represent a potential novel therapeutic agent for treatment of C. albicans infection in combination with existing clinical antifungals.

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Candida glabrata: A Lot More Than Meets the Eye

Microorganisms ◽

10.3390/microorganisms7020039 ◽

2019 ◽

Vol 7 (2) ◽

pp. 39 ◽

Cited By ~ 18

Author(s):

Kundan Kumar ◽

Fizza Askari ◽

Mahima Sahu ◽

Rupinder Kaur

Keyword(s):

Fungal Pathogen ◽

Biofilm Formation ◽

Candida Glabrata ◽

External Environment ◽

Bloodstream Infections ◽

Yeast Saccharomyces Cerevisiae ◽

Pathogenic Yeast ◽

Human Fungal Pathogen ◽

Life Threatening ◽

Inflammatory Immune Response

Candida glabrata is an opportunistic human fungal pathogen that causes superficial mucosal and life-threatening bloodstream infections in individuals with a compromised immune system. Evolutionarily, it is closer to the non-pathogenic yeast Saccharomyces cerevisiae than to the most prevalent Candida bloodstream pathogen, C. albicans. C. glabrata is a haploid budding yeast that predominantly reproduces clonally. In this review, we summarize interactions of C. glabrata with the host immune, epithelial and endothelial cells, and the ingenious strategies it deploys to acquire iron and phosphate from the external environment. We outline various attributes including cell surface-associated adhesins and aspartyl proteases, biofilm formation and stress response mechanisms, that contribute to the virulence of C. glabrata. We further discuss how, C. glabrata, despite lacking morphological switching and secreted proteolytic activity, is able to disarm macrophage, dampen the host inflammatory immune response and replicate intracellularly.

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