Epidemiological Assessment and Risk Factors for Mortality of Bloodstream Infections by Candida sp. and the Impact of the COVID-19 Pandemic Era.

Candidemia is one of the healthcare-associated infections that has high mortality. The risk factors that predispose a patient to develop this infection are mostly found in patients of greater severity and COVID-19 contributes to the risk of death. The aim of this study is to evaluate epidemiological characteristics and risk factors for mortality in patients with candidemia before and during the COVID-19 pandemic era. This is a retrospective study conducted at Instituto Central from 2016 to 2020 of patients with candidemia that were evaluated for demographic data, medical history, risk factors, microbiological data, therapeutic measures, complementary exams, device management, and outcome defined by 30-day mortality. A total of 170 episodes were included (58.2% males; mean age of 56 years). The overall incidence density of candidemia per 1000 admissions and per 1000 patient-days was 1.17 and 0.17, respectively, with an increase of 38% in the year 2020. The use of a central venous catheter was the most prevalent (93.5%) condition, followed by the previous use of antibiotics (91.1%). Corticosteroid use ranked seventh (56.4%). C. albicans was responsible for 71 (41.7%) of the isolates, followed by C. tropicalis and C. glabrata, with 34 (20%) isolates each. Echinocandin was prescribed in 60.1% of cases and fluconazole in 37%. Echocardiography resulted in six (5.08%) cases of endocarditis and fundoscopy resulting in two (2.4%) endophthalmitis. The 30-day mortality was 93/170 (54.7%). The risk factors associated with mortality were age (OR 1.03, CI 95% 1.01-1.06), heart disease (OR 7.51, CI 95% 1.48-37.9), hemodialysis (OR 3.68, CI 95% 1.28-10.57), and use of corticosteroids (OR 2.83, CI 95% 1.01-7.92). The COVID-19 pandemic had an impact on the increase incidence of candidemia. The persistently high mortality highlights the need for better management strategies, control of risk factors, and guarantee of adequate treatment.

Is the C-Terminal Domain an Effective and Selective Target for the Design of Hsp90 Inhibitors against Candida Yeast?

Improving the armamentarium to treat invasive candidiasis has become necessary to overcome drug resistance and the lack of alternative therapy. In the pathogenic fungus Candida albicans, the 90-kDa Heat-Shock Protein (Hsp90) has been described as a major regulator of virulence and resistance, offering a promising target. Some human Hsp90 inhibitors have shown activity against Candida spp. in vitro, but host toxicity has limited their use as antifungal drugs. The conservation of Hsp90 across all species leads to selectivity issues. To assess the potential of Hsp90 as a druggable antifungal target, the activity of nine structurally unrelated Hsp90 inhibitors with different binding domains was evaluated against a panel of Candida clinical isolates. The Hsp90 sequences from human and yeast species were aligned. Despite the degree of similarity between human and yeast N-terminal domain residues, the in vitro activities measured for the inhibitors interacting with this domain were not reproducible against all Candida species. Moreover, the inhibitors binding to the C-terminal domain (CTD) did not show any antifungal activity, with the exception of one of them. Given the greater sequence divergence in this domain, the identification of selective CTD inhibitors of fungal Hsp90 could be a promising strategy for the development of innovative antifungal drugs.

Oteseconazole: a long-awaited diversification of the antifungal arsenal to manage recurrent vulvovaginal candidiasis (RVVC).

INTRODUCTION: Recurrent vulvovaginal candidiasis (RVVC) affects women worldwide and has far-reaching implications for a patient's quality of life. For decades, maintenance treatment using the azole antifungal fluconazole was the preferred treatment. Although efficient in controlling the symptoms, the development of azole resistance and high rates of recurrence after therapy cessation have emerged as significant limitations. Nevertheless, persistent efforts have delivered novel treatment options. Oteseconazole (VT-1161), marketed as VIVJOA, is an oral, tetrazole antifungal with unprecedented specificity toward the fungal lanosterol 14α-demethylase. AREAS COVERED: We reviewed literature data on oteseconazole with a focus on the management of RVVC. EXPERT OPINION: Therapeutic options for RVVC are limited, and novel, innovative approaches are needed to treat this debilitating condition. These therapies need to be well-tolerated and prevent RVVC recurrence. The available clinical data show excellent safety and efficacy, with an unprecedentedly low recurrence rate. However, we believe health-care providers should be mindful to monitor for the development of resistance, as this may result in treatment failure. Further, the availability and cost may, like for most novel drugs, affect the widespread clinical implementation of VIVJOA. Altogether, we are convinced that VIVJOA is a significant advance in RVVC management.

Biosurfactant from Candida: sources, classification, and emerging applications.

Biosurfactants are surface-active molecules that are synthesized by many microorganisms like fungi, bacteria, and yeast. These molecules are amphiphilic in nature, possessing emulsifying ability, detergency, foaming, and surface-activity like characteristics. Yeast species belongs to the genus Candida has gained globally enormous interest because of the diverse properties of biosurfactants produced by theme. In contrast to synthetic surfactants, biosurfactants are claimed to be biodegradable and non-toxic which labels them as a potent industrial compound. Biosurfactants produced by this genus are reported to possess certain biological activities, such as anticancer and antiviral activities. They also have potential industrial applications in bioremediation, oil recovery, agricultural, pharmaceutical, biomedical, food, and cosmetic industries. Various species of Candida have been recognized as biosurfactant producers, including Candida petrophilum, Candida bogoriensis, Candida antarctica, Candida lipolytica, Candida albicans, Candida batistae, Candida albicans, Candida sphaerica, etc. These species produce various forms of biosurfactants, such as glycolipids, lipopeptides, fatty acids, and polymeric biosurfactants, which are distinct according to their molecular weights. Herein, we provide a detailed overview of various types of biosurfactants produced by Candida sp., process optimization for better production, and the latest updates on the applications of these biosurfactants.

Preparation of functional oils rich in diverse medium and long-chain triacylglycerols based on a broadly applicable solvent-free enzymatic strategy.

To address the problems of long reaction times and limited range of adaptation in enzymatic synthesis medium- and long-chain triacylglycerols (MLCTs), a broadly applicable solvent-free enzymatic interesterification strategy was proposed. Candida sp. lipase (CSL) was immobilized on hydrophobic hollow mesoporous silica spheres (HHSS) to construct a biocatalyst designated as CSL@HHSS with a 15.3 % immobilization yield and a loading amount of 94.0 mg/g. The expressed activity and the specific activity were 20.14 U/g and 173.62 U/g, which were 4.6 and 5.6 times higher than that of free CSL, respectively. This biocatalyst demonstrated higher activity, wider applicability, and excellent reusability. Linseed oil, sunflower oil, perilla seed oil, algal oil, and malania oleifera oil were applied as substrates to produce MLCTs with medium-chain triacylglycerols (MCT) catalyzed by CSL@HHSS through interesterification in yields ranging from 69.6 % to 78.0 % within 20 min. Specific fatty acids, including linolenic acid, oleic acid, DHA, and nervonic acid (the first reported), were introduced into MLCT's skeleton, respectively. The structures were finely analyzed and identified by GC and UPLC-MS. The catalytic efficiency value of CSL@HHSS in catalyzing interesterification between linseed oil and MCT (70 ℃, 20 min, lipase 6 wt%) is 0.86 g/g∙min, which is the highest ever reported. This paper presents an effective and sustainable strategy for functional MLCTs production.

Antifungal Activity of Mycogenic Silver Nanoparticles on Clinical Yeasts and Phytopathogens.

In this study, seven different silver nanoparticles (AgNPs) were obtained using the fungi species from the phylum Ascomycota, Aspergillus tubingensis, Aspergillus spp., Cladosporium pini-ponderosae, Fusarium proliferatum, Epicoccum nigrum, Exserohilum rostratum, and Bionectria ochroleuca, isolated from the Brazilian biodiversity, particularly from the mangrove and Caatinga biomes. The nanoparticles were coded as AgNP-AT, AgNP-Asp, AgNP-CPP, AgNP-FP, AgNP-EN, AgNP-ER, and AgNP-BO and characterized using spectrophotometry (UV-Vis), dynamic light scattering (DLS), zeta potential, transmission electron microcopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy. All the AgNPs presented homogeneous size in the range from 43.4 to 120.6 nm (DLS) and from 21.8 to 35.8 nm (TEM), pH from 4.5 to 7.5, negative charge, and presence of protein coating on their surface. The antifungal activity of the AgNPs was evaluated on clinical strains of Candida albicans, and on the non-albicans species, Candida krusei, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Candida guilliermondii, common in hospital infections, and against the phytopathogens Fusarium oxysporum, Fusarium phaseoli, Fusarium sacchari, Fusarium subglutinans, Fusarium verticillioides, and Curvularia lunata, which are species responsible for serious damage to agriculture production. The AgNPs were effective against the yeasts with MICs ranging from 1.25 to 40 µM and on the phytopathogens with MICs from 4 to 250 µM, indicating the promising possibility of application of these AgNPs as antifungal agents. The results indicated that the physicochemical parameters of the AgNPs, including the functional groups present on their surface, interfered with their antifungal activity. Overall, the results indicate that there is no specificity of the AgNPs for the yeasts or for the phytopathogens, which can be an advantage, increasing the possibility of application in different areas.

A novel and controllable method for simultaneous preparation of human milk fat substitutes (OPL, OPO and LPL): two-step enzymatic ethanolysis-esterification strategy.

A novel and effective approach based on the two-step ethanolysis-esterification strategy was proposed for the controllable and simultaneous preparation of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL), 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) and 1,3-dilinoleoyl-2-palmitoyl-glycerol (LPL) with adjustable proportions. Enzymatic ethanolysis of fractionated palm stearin was carried out to yield 2-monopalmitoylglycerol (79.4 ± 0.6 %) with over 91.0 % purity at the optimal conditions. The immobilized Candida sp. lipase (CSL) on octyl-functionalized ordered mesoporous silica (OMS-C8) was applied to re-esterify 2-monopalmitoylglycerol with oleic acid and linoleic acid for the simultaneous production of OPL, OPO, and LPL. The total content in the final products was 81.5 %, with 91.3 % of palmitic acid (PA) content at the sn-2 position. Besides, OPL/OPO/LPL was conveniently prepared with suitable proportions for worldwide infants by adjusting the ratio of acyl donors. This paper provides a novel and effective two-step ethanolysis-esterification strategy for the development of human milk fat substitutes (HMFS).

Antifungal activity of mycogenic silver nanoparticles on clinical yeasts and phytopathogens

In this study, seven different silver nanoparticles (AgNPs) were obtained using the fungi species from the phylum Ascomycota, Aspergillus tubingensis, Aspergillus spp., Cladosporium pini-ponderosae, Fusarium proliferatum, Epicoccum nigrum, Exserohilum rostratum, and Bionectria ochroleuca, isolated from the Brazilian biodiversity, particularly from the mangrove and Caatinga biomes. The nanoparticles were coded as AgNP-AT, AgNP-Asp, AgNP-CPP, AgNP-FP, AgNP-EN, AgNP-ER, and AgNP-BO and characterized using spectrophotometry (UV-Vis), dynamic light scattering (DLS), zeta potential, transmission electron microcopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy. All the AgNPs presented homogeneous size in the range from 43.4 to 120.6 nm (DLS) and from 21.8 to 35.8 nm (TEM), pH from 4.5 to 7.5, negative charge, and presence of protein coating on their surface. The antifungal activity of the AgNPs was evaluated on clinical strains of Candida albicans, and on the non-albicans species, Candida krusei, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Candida guilliermondii, common in hospital infections, and against the phytopathogens Fusarium oxysporum, Fusarium phaseoli, Fusarium sacchari, Fusarium subglutinans, Fusarium verticillioides, and Curvularia lunata, which are species responsible for serious damage to agriculture production. The AgNPs were effective against the yeasts with MICs ranging from 1.25 to 40 µM and on the phytopathogens with MICs from 4 to 250 µM, indicating the promising possibility of application of these AgNPs as antifungal agents. The results indicated that the physicochemical parameters of the AgNPs, including the functional groups present on their surface, interfered with their antifungal activity. Overall, the results indicate that there is no specificity of the AgNPs for the yeasts or for the phytopathogens, which can be an advantage, increasing the possibility of application in different areas.

Effect of fixed orthodontic appliances on gingival status and oral microbiota: a pilot study.

BACKGROUND: This pilot study aimed to investigate how fixed orthodontic appliances simultaneously applied on the upper and lower arches affect the oral environment in the medium term. METHODS: The oral status of 30 orthodontic patients was evaluated using the number of decay-missing-filled teeth (DMFT), plaque (PI), and gingival indices (GI) before bonding of fixed orthodontic appliances (T0) and during the therapy (T1). Besides, the gingival crevicular fluid (GCF) and a dental plaque were collected. Samples were analyzed for selected Candida sp. and for 10 selected oral bacteria using mass spectroscopy and multiplex polymerase chain reaction, respectively. RESULTS: In 60% of patients, deterioration of the oral status (demonstrated by the increase in PI) was recorded (p < 0.05). Moreover, the changes in PI correlated with those of GI (p < 0.001). At the T1 time point, the mean representation of Actinomyces sp. in the total prokaryotic DNA in GCF and dental plaque of individual patients increased compared to T0 (p < 0.05). The probability of finding any of the 7 selected periodontal bacteria combined with Candida sp. was 10 times higher in patients in whom PI deteriorated between T0 and T1 (p < 0.01). CONCLUSIONS: Changes in the oral microbial diversity and an increase in PI were observed in the medium term after bonding of orthodontic appliance. Our study highlights the importance of a complex approach in this type of research as the association between clinical characteristics and combined microbial parameters is higher than when evaluated separately.

Advanced simultaneous nitrogen and phosphorus removal for non-sterile wastewater through a novel coupled yeast-sludge system: Performance, microbial interaction, and mechanism.

A novel coupled yeast-sludge system (CYSS) was constructed by the yeast Candida sp. PNY integrated with activated sludge to treat non-sterile mainstream wastewater. After 240-day cultivation, compared with single activated sludge, simultaneous removal efficiency of total organic carbon (TOC), nitrogen and phosphorus increased by 19.5% (176.34 mg TOC g-1 d-1), 21.3% (11.25 mg TN g-1 d-1) and 15.0% (6.95 mg TP g-1 d-1), respectively, while the amount of sludge reduced by 50%. Amplicon sequencing analysis showed that the abundance of Nitrosomonas, Nitrospira, Zoogloea, Dechloromonas, and Candidatus Accumulibacter significantly decreased to 0% on Day 200. Abundance of nirS and nirK for denitrification significantly decreased in CYSS by quantitative PCR (qPCR), and the copies of nirS and nirK were 3.37-fold and 1.71-fold decrease from Day 0 to Day 240, respectively. The results of Fluorescence in situ hybridization and co-occurrence network showed that Candida sp. PNY predominated its distribution in CYSS, and strongly connected with environmental variables based on network analysis. Furthermore, this study reconstructed the carbon, nitrogen and phosphorus metabolic pathways of the CYSS based on metagenomics.

Candida species and selected behavioral factors co-associated with severe early childhood caries: Case-control study.

Severe Early Childhood Caries (sECC) is a multifactorial disease associated with the occurrence of specific oral microorganisms and other environmental, behavioral, and genetic factors. This study aimed to construct a multivariable model including the occurrence of Candida spp. and selected behavioral factors (length of breastfeeding, serving sweet beverages and beginning of brushing child's teeth) to determine their relationships to the occurrence of sECC. In this case-control study 164 children with sECC and 147 children without dental caries were included. MALDI-TOF MS and multiplex qPCR were used to identify Candida spp. and selected bacteria in dental plaque samples, respectively. A questionnaire on oral hygiene, diet, and children's health was filled in by the parents. The constructed multivariable logistic regression model showed an independent influence of the microbial and behavioral factors in sECC etiopathogenesis. The occurrence of C. albicans and C. dubliniensis was associated with higher odds of sECC development (odds ratio, OR: 9.62 and 16.93, respectively), together with breastfeeding of 6 months or less (OR: 2.71), exposure to sweet beverages (OR: 3.77), and starting to brush child's teeth after the 12th month of age (OR: 4.10), all statistically significant (p < 0.01). Considering the high occurrence of C. albicans and C. dubliniensis in dental plaque in children with sECC, we propose them as "keystone pathogens" and risk factors for sECC. The models showed that presence of specific species of Candida in dental plaque may be a better descriptor of sECC than the mentioned behavioral factors.

Enhanced antioxidant capacity of lipoic acid in different food systems through lipase-mediated esterification with phytosterols.

BACKGROUND: α-Lipoic acid has excellent antioxidant activity, but its poor lipid solubility greatly limits its practical application. This study was undertaken (i) to develop a novel and efficient enzymatic synthesis of lipophilic lipoic acid esters using Candida sp. 99-125 lipase as a catalyst; and (ii) to systematically evaluate their antioxidant potential against bulk oil, oil-in-water emulsion (O/W) and cooked ground meat. RESULTS: Lipophilic lipoic acid esters were successfully and efficiently synthesized using phytosterols as acyl receptor in the presence of Candida sp. 99-125 lipase. The product was identified as phytosterol lipoate by mass spectrometry, Fourier transform infrared spectroscopy and nuclear magnetic resonance. The maximum conversion of phytosterol lipoate surpassed 90% within 12 h and its final yield exceeded 81%. Interestingly, the oil solubility of lipoic acid was increased at least 25-fold and other physicochemical properties were significantly improved. Most importantly, phytosterol lipoate exhibited higher antioxidant activity than lipoic acid in bulk oil, O/W emulsions and cooked ground meat. CONCLUSION: The antioxidant capacity of lipoic acid can be significantly enhanced by esterification with phytosterols. Therefore, phytosterol lipoate could be further developed as a new antioxidant for use in oil- and fat-based foods. © 2022 Society of Chemical Industry.

Evaluation of anticandidal activities and phytochemical examination of extracts prepared from Vitex agnus-castus: a possible alternative in treating candidiasis infections.

BACKGROUND: Candidiasis infection is associated with high morbidity and mortality. Fungicidal resistance of some commercially used fungicides ascended the need for a naturally effective alternative. The current study aimed to evaluate the fungicidal activity of Vitex agnus-castus extracts in vitro against some Candida species. METHODS: The bioactive compounds contained in the crude and alcoholic extracts were compared, and the antioxidant activity was tested, as well. The phytochemical analysis was carried out by Fourier Transform-Infrared Spectroscopy (FTIR) and Gas Chromatography-Mass Spectrometry (GC/MS). The scavenger activity of the tested extracts was tested, as well. The anticandidal activity was tested to detect the effect of the tested extracts on the mycelial growth of Candida albicans, Candida krusei, Candida parapsilosis, Candia tropicalis, Candida famata, Candida rhodotorula, and Candida dublinesis. The minimum inhibitory concentrations were calculated for all reported activities. The Scanning Electron Microscopy (SEM) and the Transmission Electron Microscopy (TEM) were used to detect the morphological and ultrastructure response in some selected species. RESULTS: FTIR and GC/MS revealed the existence of different bioactive chemical groups such as polyphenols, fatty acids, terpenes, terpenoids, steroids, aldehydes, alcohols, and esters, phytol which is a diterpene. DPPH results confirmed the antioxidant activity of all extracts where the methanolic extract was the strongest scavenging substrate. All extracts showed strong inhibitory effects against different species at a concentration of 200 µg/ml (P < 0.001). SEM and TEM showed morphological and ultrastructure changes in C. famata. CONCLUSION: The current study suggested a reliable antifungal activity of different extracts of Vitex agnus-castus against different Candida species and strains. However, further studies are required to confirm the safety of these extracts to be used in medical applications.

Evaluation of Indigenous Candida oleophila and Candida boidinii in Monoculture and Sequential Fermentations: Impact on Ethanol Reduction and Chemical Profile in Chilean Sauvignon Blanc Wines.

The study of non-Saccharomyces yeasts in wine fermentations allows the exploration of new alternatives for the reduction of ethanol in wines. The objective of this work was to evaluate the fermentation capacity of two indigenous Candida yeasts (C. oleophila and C. boidinii) in monoculture and sequential fermentations (laboratory and microvinification scale) to produce Chilean Sauvignon Blanc wine. Fermentations were monitored by the determination of ethanol, glycerol, organic acids, and residual sugars. The results indicated that at the laboratory scale for both the monoculture and sequential fermentations it was possible to reduce the ethanol concentration on 0.77% v/v (monoculture) and 1.5% v/v (sequential) for C. oleophila and 0.50% v/v (monoculture) and 0.04% v/v (sequential) for C. boidinii compared to S. cerevisiae (12.87% v/v). Higher glycerol concentrations were produced in monoculture than sequential fermentations (C. oleophila: 9.47 g/L and C. boidinii 10.97 g/L). For microvinifications, the monoculture and sequential fermentations with C. boidinii managed to reduce ethanol content by 0.17% v/v and 0.54% v/v, respectively, over the S. cerevisiae control (13.74% v/v). In the case of C. oleophila, the reduction was only observed in sequential fermentations with 0.62% v/v. Interestingly, grapes with higher sugar concentration resulted in wines with lees ethanol concentrations. This might be associated to the use of C. oleophila (13.12% v/v) and C. boidinii (13.20% v/v) in sequential fermentations microvinification scale.

Synthesis and Evaluation of the Antifungal and Toxicological Activity of Nitrofuran Derivatives.

Fungal diseases affect more than 1 billion people worldwide. The constant global changes, the advent of new pandemics, and chronic diseases favor the diffusion of fungal pathogens such as Candida, Cryptococcus, Aspergillus, Trichophyton, Histoplasma capsulatum, and Paracoccidioides brasiliensis. In this work, a series of nitrofuran derivatives were synthesized and tested against different fungal species; most of them showed inhibitory activity, fungicide, and fungistatic profile. The minimal inhibitory concentration (MIC90) values for the most potent compounds range from 0.48 µg/mL against H. capsulatum (compound 11) and P. brasiliensis (compounds 3 and 9) to 0.98 µg/mL against Trichophyton rubrum and T. mentagrophytes (compounds 8, 9, 12, 13 and 8, 12, 13, respectively), and 3.9 µg/mL against Candida and Cryptococcus neoformans strains (compounds 1 and 5, respectively). In addition, all compounds showed low toxicity when tested in vitro on lung cell lines (A549 and MRC-5) and in vivo in Caenorhabditis elegans larvae. Many of them showed high selectivity index values. Thus, these studied nitrofuran derivatives proved to be potent against different fungal species, characterized by low toxicity and high selectivity; for these reasons, they may become promising compounds for the treatment of mycoses.

Heavy metal-induced oxidative stress and alteration in secretory proteins in yeast isolates.

In the recent years, yeasts have evolved as potent bioremediative candidates for the detoxification of xenobiotic compounds found in the natural environment. Candida sp. are well-studied apart from Saccharomyces sp. in heavy metal detoxification mechanisms. In the current study, Candida parapsilosis strain ODBG2, Candida sp. strain BANG3, and Candida viswanathii strain ODBG4 were isolated from industrial effluents and contaminated ground water, and were studied for their metal tolerance. Among these three isolates, the metal tolerance was found to be more towards Lead (Pb 2 mM), followed by Cadmium (Cd 1.5 mM) and Chromium [Cr(VI), 1 mM]. On further exploring the involvement of primary defensive enzymes in these isolates towards metal tolerance, the anti-oxidative enzyme superoxide dismutase was found to be prominently high (25% with respect to the control) during first 24 h of metal-isolate interaction. The Catalase enzyme assay was observed to have increased enzyme activity at 48 h. It also triggered the activity of peroxidases, which lead to the increase in reduced glutathione in the organism by 0.87-1.9-fold as a metal chelator and also as a second-line defensive molecule. The exoproteome profile showed the early involvement (exponential growth phase) of secreted proteins (low-molecular-weight) of about ~ 40-45 kDa under Cd and Pb stress (0.5 mM). The exoproteome profiling under heavy metal stress in Candida parapsilosis strain ODBG2 and Candida viswanathii strain ODBG4 is the first report.

Phytoproduct, Arabic Gum and Opophytum forsskalii Seeds for Bio-Fabrication of Silver Nanoparticles: Antimicrobial and Cytotoxic Capabilities.

The application of biological materials in synthesizing nanoparticles has become significant issue in nanotechnology. This research was designed to assess biogenic silver nanoparticles (AgNPs) fabricated using two aqueous extracts of Acacia arabica (Arabic Gum) (A-AgNPs) and Opophytum forsskalii (Samh) seed (O-AgNPs), which were used as reducing and capping agents in the NPs development, respectively. The current study is considered as the first report for AgNP preparation using Opophytum forsskalii extract. The dynamic light scattering, transmission electron microscopy, and scanning electron microscopy were employed to analyze the size and morphology of the biogenic AgNPs. Fourier transform infrared (FTIR) spectroscopy and chromatography/mass spectrometry (GC-MS) techniques were used to identify the possible phyto-components of plant extracts. The phyto-fabricated NPs were assessed for their antibacterial activity and also when combined with some antibiotics against Staphylococcus aureus (Gram-positive) and Pseudomonas aeruginosa and Escherichia coli (Gram-negative) and their anticandidal ability against Candida albicans using an agar well diffusion test. Furthermore, cytotoxicity against LoVo cancer cell lines was studied. The results demonstrated the capability of the investigated plant extracts to change Ag+ ions into spherical AgNPs with average size diameters of 91 nm for the prepared O-AgNPs and 75 nm for A-AgNPs. The phyto-fabricated AgNPs presented substantial antimicrobial capabilities with a zone diameter in the range of 10-29.3 mm. Synergistic effects against all tested strains were observed when the antibiotic and phyto-fabricated AgNPs were combined and assessed. The IC50 of the fabricated O-AgNPs against LoVo cancer cell lines was 28.32 µg/mL. Ten and four chemical components were identified in Acacia arabica (Arabic Gum) and Opophytum forsskalii seed extracts, respectively, by GC-MS that are expected as NPs reducing and capping agents. Current results could lead to options for further research, such as investigating the internal mechanism of AgNPs in bacteria, Candida spp., and LoVo cancer cell lines as well as identifying specific molecules with a substantial impact as metal-reducing agents and biological activities.

The Role of the Oral Microbiota in the Etiopathogenesis of Oral Squamous Cell Carcinoma.

Dysbiosis in the oral environment may play a role in the etiopathogenesis of oral squamous cell carcinoma (OSCC). This review aims to summarize the current knowledge about the association of oral microbiota with OSCC and to describe possible etiopathogenetic mechanisms involved in processes of OSCC development and progression. Association studies included in this review were designed as case-control/case studies, analyzing the bacteriome, mycobiome, and virome from saliva, oral rinses, oral mucosal swabs, or oral mucosal tissue samples (deep and superficial) and comparing the results in healthy individuals to those with OSCC and/or with premalignant lesions. Changes in relative abundances of specific bacteria (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus sp.) and fungi (especially Candida sp.) were associated with OSCC. Viruses can also play a role; while the results of studies investigating the role of human papillomavirus in OSCC development are controversial, Epstein-Barr virus was positively correlated with OSCC. The oral microbiota has been linked to tumorigenesis through a variety of mechanisms, including the stimulation of cell proliferation, tumor invasiveness, angiogenesis, inhibition of cell apoptosis, induction of chronic inflammation, or production of oncometabolites. We also advocate for the necessity of performing a complex analysis of the microbiome in further studies and of standardizing the sampling procedures by establishing guidelines to support future meta-analyses.

Herbal Products and Their Active Constituents Used Alone and in Combination with Antifungal Drugs against Drug-Resistant Candida sp.

Clinical isolates of Candida yeast are the most common cause of opportunistic fungal infections resistant to certain antifungal drugs. Therefore, it is necessary to detect more effective antifungal agents that would be successful in overcoming such infections. Among them are some herbal products and their active constituents.The purpose of this review is to summarize the current state of knowledge onherbal products and their active constituents havingantifungal activity against drug-resistant Candida sp. used alone and in combination with antifungal drugs.The possible mechanisms of their action on drug-resistant Candida sp. including (1) inhibition of budding yeast transformation into hyphae; (2) inhibition of biofilm formation; (3) inhibition of cell wall or cytoplasmic membrane biosynthesis; (4) ROS production; and (5) over-expression of membrane transporters will be also described.

Raw bovine milk as a reservoir of yeast with virulence factors and decreased susceptibility to antifungal agents.

In recent years, increased rates of yeast infections in humans and animals have been recognized worldwide. Since animals may represent a source of yeast infections for humans, knowing the antifungal susceptibility profile of yeast isolates from milk and evaluating their pathogenic potential would be of great medical importance. Therefore, the aim of this survey was to study yeast diversity in milk samples, analyze the hemolytic and phospholipase activities of isolates and determine minimal inhibition concentration (MIC) for fluconazole, voriconazole and flucytosine. Out of 66 yeast isolates obtained from 910 individual raw milk samples from subclinically infected cows, 26 different yeast species were determined based on sequencing of the D1/D2 and ITS regions. Among them, Pichia kudriavzevii (formerly known as Candida krusei), Kluyveromyces marxianus (formerly known as Candida kefyr) and Debaryomyces hansenii (formerly known as Candida famata) were the most commonly identified. Hemolysin and/or phospholipase activity was observed in 66.7% of isolates. The elevated MIC for fluconazole was determined in 16 isolates from 11 species. The findings of this study demonstrate that yeast isolates from raw milk have the potential to express virulence attributes such as hemolysin and phospholipase, and additionally, some of these strains showed elevated MIC to fluconazole or to flucytosine. LAY SUMMARY: We identified 66 yeast isolates, including 26 different yeast species from 910 individual milk samples. Our results indicate that individual milk samples may serve as a source of yeasts with the potential to trigger infection and may have reduced sensitivity to tested antifungal agents.