Candidemia and its risk factors in neonates and children

Objectives: The present study was conducted to raise attention to the frequency of Candida spp. and evaluation of risk factors of candidemia in hospitalized neonates and children. Methods: Identification of Candida at species level was done using the PCR-RFLP method. The Candida albicans complex and Candida parapsilosis complex were differentiated using the HWP1 gene amplification and PCR-RFLP with NlaIII restriction enzyme, respectively. Results: Out of 75 blood culture specimens, 42 (84) cases were positive for Candida spp. of whom 30 (71.42) and 12 (28.57) cases were female and male, respectively. Thirty-two (76) candidemia were presented in pediatrics with 6 years up to 12 years, 10 (23.80) in neonates of one month or less. In the present study, Candida parapsilosis (n =25; 59.52) was the most prevalent isolated species followed by C. albicans (n =11; 26.19), C. tropicalis (n =4; 9.52), and Candida glabrata (n =2; 4.76). Conclusions: According to potentially dangerous complications of bloodstream infection by Candida spp. in neonates and children, it is necessary to identify and eliminate the underlying conditions and risk factors of this disease. © 2020, Author(s)

Voriconazole resistance genes in Aspergillus flavus clinical isolates

Objective: The present study was designed to discover novel biomarkers involved in voriconazole resistance in clinical isolates of Aspergillus flavus. Materials and methods: Two voriconazole non-wild-type and two voriconazole-wild-type A. flavus clinical isolates were selected to evaluate possible molecular mechanism involved in A. flavus resistance to voriconazole using the mutation assessment, Quantitative real- time PCR of cyp51A and cyp51C genes and complementary DNA- amplified fragment length polymorphism technique. Results: No mutations were seen in the cyp51A and cyp51C genes in voriconazole non-wild-type isolates compared to wild- type and reference strains. Regarding to mRNA expression results, no changes were observed in expression fold of cyp51A and cyp51C mRNA expression level in first non- wild- type isolate compared to wild-type isolate. For second isolate cyp51C mRNA expression level was down regulated (5.6 fold). The set of genes including ABC fatty acid transporter XM- 002375835 and aldehydereductase XM- 002376518 and three unknown functional genes were identified. Based on results, the over-expression of AKR1 and ABC fatty acid transporter in the voriconazole non- wild- type isolates suggests these genes could represent a novel molecular marker linked to the voriconazole resistance in A. flavus. Conclusion: The results obtained in this study showed a novel finding as the authors identified AKR1 and ABC fatty acid transporter genes as possible voriconazole target genes in Iranian clinical isolates of A. flavus. © 202

Voriconazole resistance genes in Aspergillus flavus clinical isolates

Objective. - The present study was designed to discover novel biomarkers involved in voriconazole resistance in clinical isolates of Aspergillus flavus. Materials and methods. - Two voriconazole non-wild-type and two voriconazole-wild-type A. flavus clinical isolates were selected to evaluate possible molecular mechanism involved in A.flavus resistance to voriconazole using the mutation assessment, Quantitative real- time PCR of cyp51A and cyp51C genes and complementary DNA- amplified fragment length polymorphism technique. Results. - No mutations were seen in the cyp51A and cyp51C genes in voriconazole non-wild-type isolates compared to wild- type and reference strains. Regarding to mRNA expression results, no changes were observed in expression fold of cyp51A and cyp51C mRNA expression level in first non- wild- type isolate compared to wild-type isolate. For second isolate cyp51C mRNA expression level was down regulated (5.6 fold). The set of genes including ABC fatty acid transporter XM- 002375835 and aldehydereductase XM- 002376518 and three unknown functional genes were identified. Based on results, the over-expression of AKR1 and ABC fatty acid transporter in the voriconazole non- wild- type isolates suggests these genes could represent a novel molecular marker linked to the voriconazole resistance in A. flavus. Conclusion. - The results obtained in this study showed a novel finding as the authors identified AKR1 and ABC fatty acid transporter genes as possible voriconazole target genes in Iranian clinical isolates of A. flavus. (C) 2020 Published by Elsevier Masson SAS

Microbiological detoxification of mycotoxins: Focus on Mechanisms and Advances

Some fungal species of the genera Aspergillus, Penicillium, and Fusarium secretes toxic metabolites known as mycotoxins, has become a global concern that is toxic to different species of animals and humans. Biological mycotoxins detoxification has been studied by researchers around the world as a new strategy for the mycotoxin removal. Bacteria, fungi, yeast, molds, and protozoa are the main living organisms appropriate for the mycotoxin detoxification. Enzymatic and degradation sorption are the main mechanisms involved in microbiological detoxification of mycotoxins. Regardless of the method used, proper management tools that consist of before-harvest prevention and after-harvest detoxification, are required. Here, in this review we focus on the microbiological detoxification, and mechanisms involved in decontamination of mycotoxins

Ocular Fungi: Molecular Identification and Antifungal Susceptibility Pattern to Azoles

Background: Treatment of ocular infection by fungi has become a problematic issue, particularly in deep lesion cases, because of the limited available antifungals and emerging resistance species. Objectives: The present study was designed for molecular identification and studying the antifungal susceptibility pattern of ocular fungi. Methods: Fifty-three ocular fungal isolates, including Fusarium spp., Aspergillus spp., yeast spp., and dematiaceous fungi were collected. Initial identification of each sample was performed using routine mycological techniques. ITS1-5.8SrDNA-ITS2 and translation elongation factor (TEF)-1 alpha regions were used for the identification and differentiation of ocular non-Fusarium and Fusarium fungal species, respectively. The antifungal susceptibility of itraconazole, voriconazole, and posaconazole was determined according to the CLSI guidelines (CLSI M38 and M60, 3rd ed.) for filamentous and yeast species, respectively. Results: Voriconazole and posaconazole showed excellent activity in all tested isolates; however, some of Fusarium, Aspergillus, and Curvularia strains showed minimum inhibitory concentration (MIC) >= 2 mu g/mL. The itraconazole showed different results in all species, and high MICs (>= 16 mu g/mL) were found. Conclusions: Finally, in the present study, we tried to identify species involved in fungal ocular infection using the molecular methods, which highlighted the importance of precise identification of species to choose an appropriate antifungal regime. On the other hand, our findings showed that antifungal susceptibility test is effective to reliably predict the in vivo response to therapy in infections; however, in fungal ocular infection cases, the penetration of antifungals may contribute to predict the outcome

Design, Synthesis, and in Vitro and in Vivo Evaluation of Novel Fluconazole-Based Compounds with Promising Antifungal Activities

Demand has arisen for developing new azole antifungal agents with the growth of the resistant rate of infective fungal species to current azole antifungals in recent years. Accordingly, the present study reports the synthesis of novel fluconazole (FLC) analogues bearing urea functionality that led to discovering new azole agents with promising antifungal activities. In particular, compounds 8b and 8c displayed broad-spectrum activity and superior in vitro antifungal capabilities compared to the standard drug FLC against sensitive and resistant Candida albicans (C. albicans). The highly active compounds 8b and 8c had potent antibiofilm properties against FLC-resistant C. albicans species. Additionally, these compounds exhibited very low toxicity for three mammalian cell lines and human red blood cells. Time-kill studies revealed that our synthesized compounds displayed a fungicidal mechanism toward fungal growth. Furthermore, a density functional theory (DFT) calculation, additional docking, and independent gradient model (IGM) studies were performed to analyze their structure-activity relationship (SAR) and to assess the molecular interactions in the related target protein. Finally, in vivo results represented a significant reduction in the tissue fungal burden and improvements in the survival rate in a mice model of systemic candidiasis along with in vitro and in silico studies, demonstrating the therapeutic efficiency of compounds 8b and 8c as novel leads for candidiasis drug discovery. © 2021 The Authors. Published by American Chemical Society.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Synthesis and anti-Helicobacter pylori activity of 5-(nitroaryl)-1,3,4-thiadiazoles with certain sulfur containing alkyl side chain

A series of 5-(nitroaryl)-1,3,4-thiadiazoles bearing certain sulfur containing alkyl side chain similar to pendent residue in tinidazole molecule were synthesized and evaluated against Helicobacter pylori using disk diffusion method. The synthesized compounds were also evaluated for their antibacterial, antifungal and cytotoxic effects. Study of the structure-activity relationships of this series of compounds indicated that both the structure of the nitroaryl unit and the pendent group on 2-position of 1,3,4-thiadiazole ring dramatically impact the anti-H. pylori activity. While compound 7a containing 2-2-(ethylsulfonyl)ethylthio-side chain from nitrothiophene series was the most potent compound tested against clinical isolates of H. pylori, however, nitroimidazoles 6c and 7c were found to be more promising compounds because of their respectable anti-H. pylori activity besides less cytotoxic effects. © 2008 Elsevier Ltd. All rights reserved

Azole antifungal resistance in candida albicans and candida glabrata isolated from vulvovaginal candidiasis patients

Background: Vulvovaginal candidiasis (VVC) is the most frequent fungal disorder in healthy and normal women. Objectives: The aim of this study was to evaluate the in vitro antifungal susceptibility of clinical isolates Candida albicans and Candida glabrata, the two most common candida species in Iranian patients with VVC. Methods: One hundred and eight clinical isolates of candida, including; C. albicans (n = 77) and C. glabrata: (n = 31) were isolated from the 108 patients with VVC. The in vitro activity of caspofungin (CAS), amphotericin B (AMB), voriconazole (VRC), itraconazole (ITC), fluconazole (FLC), and nystatin (NYS) were determined according to the CLSI M27-A3 and CLSI M27-S4. Results: Our results were shown 8 (25.8 %) and 6 (7.8 %) C. glabrata and C. albicans isolates resistance to FLU, respectively. Furthermore, resistance to VRC and ITC were observed in 8.4%, and 3.7% of all isolates, and six isolates (5.6%) had intermediate MIC to CAS. Conclusions: We reported 8 (25.8 %) and 6 (7.8 %) C. glabrata and C. albicans isolates resistance to FLU, respectively. Furthermore, resistance to VRC and ITC were observed in 8.4% and 3.7% of all isolates, respectively. © 2021, Author(s)

Anti-biofilm properties of eucalyptol in combination with antifungals against Candida albicans isolates in patients with hematological malignancy

Oral candidiasis is a fungal infection caused mainly by Candida albicans and it is a major problem among hematologic malignancy patients. Biofilm formation is an attributable factor to both virulence and drug resistance of Candida species. The aim of the study was to evaluate the biofilm-producing ability of oral C. albicans isolates and to evaluate the inhibitory activity of eucalyptol on Candida biofilm, alone and in combination with antifungal agents. Samples were collected from the oral cavity of 106 patients with hematologic malignancy. The isolated yeasts were identified by PCR-sequencing. Then C. albicans isolates were analyzed for their biofilm-producing ability by crystal violet staining and MTT assay. The minimum biofilm inhibition concentrations (MBIC) of eucalyptol, amphotericin B, itraconazole, and nystatin and the in vitro interaction of eucalyptol with these drugs were tested according to CLSI-M-27-A3 protocol and checkerboard methods, respectively. From 106 patients, 50 (47.2) were confirmed for oral candidiasis mean +/- SD age 39 +/- 14 years; female 31 (62%) and male 19 (38%). C. albicans was isolated from 40 of 50 (80%) patients. From 40 C. albicans isolates, 24 (60%) and 16 (40%) were moderate and weak biofilm producer, respectively. The geometric mean MBIC of amphotericin B, itraconazole, nystatin and eucalyptol were 3.93 mu g/mL, 12.55 mu g/mL, 0.75 mu g/mL and 798 mu g/mL, respectively. Eucalyptol interacted synergistically with amphotericin B, itraconazole and nystatin against 12.5, 10, and 22.5% of isolates, respectively. Eucalyptol demonstrated promising activity against biofilm of C. albicans when tested alone or combined with antifungal drugs