Proanthocyanidins and volatile aroma of cranberry juice are modulated by its microbiota and processing environment.

The quality and sensory attributes of juices are influenced by their natural microbiota and the microorganisms found on filtration membranes. This study aimed to assess the influence of natural microbiota and specific contaminants, including Candida krusei, Rhodotorula mucilaginosa, Debaryomyces prosopidis, Ralstonia insidiosa, and Lactiplantibacillus paraplantarum, isolated from cranberry juice and its associated industrial filtration membranes, on the characteristics of cranberry juice. Their growth kinetics and impacts on total phenols, total anthocyanins, total proanthocyanins, total organic acids, pH, titratable acidity, and volatile compounds were assessed. During the 42 h fermentation period, Candida krusei and Ralstonia insidiosa exhibited significant growth, increasing by 1-log and 3-log, respectively. The natural microbiota led to a 7% and 6% reduction in anthocyanins and proanthocyanidins, while Candida krusei and Rhodotorula mucilaginosa caused losses of 10% and 7% in proanthocyanidins, respectively. Organic acid content remained stable, except for an 8% decrease caused by Ralstonia insidiosa. Volatile compounds underwent significant increases, particularly in green (703%), winey (100%), mushroom (306%), and fusel (2678%) notes. These findings underscore the rapid impact of microorganisms from natural microbiota and filtration membranes on cranberry juice characteristics, highlighting the importance for beverage industries to prioritize customer safety and satisfaction.

The antimicrobial effects of silver nanoparticles obtained through the royal jelly on the yeasts Candida guilliermondii NP-4.

The effect of silver nanoparticles (Ag NPs) obtained in the presence of royal jelly (RJ) on the growth of yeast Candida guilliermondii NP-4, on the total and H+-ATPase activity, as well as lipid peroxidation process and antioxidant enzymes (superoxide dismutase (SOD), catalase) activity was studied. It has been shown that RJ-mediated Ag NPs have a fungicide and fungistatic effects at the concentrations of 5.4 µg mL-1 and 27 µg mL-1, respectively. Under the influence of RJ-mediated Ag NPs, a decrease in total and H+-ATPase activity in yeast homogenates by ~ 90% and ~ 80% was observed, respectively. In yeast mitochondria total and H+-ATPase activity depression was detected by ~ 80% and ~ 90%, respectively. The amount of malondialdehyde in the Ag NPs exposed yeast homogenate increased ~ 60%, the catalase activity increased ~ 70%, and the SOD activity-~ 30%. The obtained data indicate that the use of RJ-mediated Ag NPs have a diverse range of influence on yeast cells. This approach may be important in the field of biomedical research aimed at evaluating the development of oxidative stress in cells. It may also contribute to a more comprehensive understanding of antimicrobial properties of RJ-mediated Ag NPs and help control the proliferation of pathogenic fungi.

Candida species-specific colonization in the healthy and impaired human gastrointestinal tract as simulated using the Mucosal Ileum-SHIME® model.

Candida species primarily exist as harmless commensals in the gastrointestinal tract of warm-blooded animals. However, they can also cause life-threatening infections, which are often associated with gut microbial dysbiosis. Identifying the microbial actors that restrict Candida to commensalism remains a significant challenge. In vitro models could enable a mechanistic study of the interactions between Candida and simulated colon microbiomes. Therefore, this study aimed to elucidate the spatial and temporal colonization kinetics of specific Candida, including C. albicans, C. tropicalis, and C. parapsilosis, and their relative Nakaseomyces glabratus, by using an adapted SHIME® model, simulating the ileum, and proximal and distal colons. We monitored fungal and bacterial colonization kinetics under conditions of eubiosis (commensal lifestyle) and antibiotic-induced dysbiosis (pathogenic lifestyle). Our findings highlighted the variability in the colonization potential of Candida species across different intestinal regions. The ileum compartment proved to be the most favourable environment for C. albicans and C. parapsilosis under conditions of eubiosis. Antibiotic-induced dysbiosis resulted in resurgence of opportunistic Candida species, especially C. tropicalis and C. albicans. Future research should focus on identifying specific bacterial species influencing Candida colonization resistance and explore the long-term effects of antibiotics on the mycobiome and bacteriome.

Anticandidal Activity of Various Probiotic Lactobacillus Strains and Their Efficacy Enhanced by Prebiotic Supplementation.

Probiotics and prebiotics have been considered as alternative approaches for promoting health. This study aimed to investigate the anticandidal potential of various probiotic Lactobacillus strains and their cell-free supernatants (CFSs). The study assessed the impact of inulin and some fruits as prebiotics on the growth of selected probiotic strains in relation to their anticandidal activity, production of short-chain fatty acids, total phenolic content, and antioxidant activity. Results revealed variations in anticandidal activity based on the specific strains and forms of probiotics used. Non-adjusted CFSs were the most effective against Candida strains, followed by probiotic cells and adjusted CFSs (pH 7). Lacticaseibacillus rhamnosus SD4, L. rhamnosus SD11 and L. rhamnosus GG displayed the strongest anticandidal activity. Non-adjusted CFSs from L. rhamnosus SD11, L. rhamnosus SD4 and L. paracasei SD1 exhibited notable anticandidal effects. The adjusted CFSs of L. rhamnosus SD11 showed the highest anticandidal activity against all non-albicans Candida (NAC) strains, whereas the others were ineffective. Supplementation of L. rhamnosus SD11 with prebiotics, particularly 2% (w/v) mangosteen, exhibited positive results in promoting probiotic growth, short-chain fatty acids production, total phenolic contents, and antioxidant activity, and the subsequent enhancing anticandidal activity against both C. albicans and NAC strains compared to conditions without prebiotics. In conclusion, both live cells and CFSs of tested strains, particularly L. rhamnosus SD11, exhibited the best anticandidal activity. Prebiotics supplementation, especially mangosteen, enhanced probiotic growth and beneficial metabolites against Candida growth. These finding suggested that probiotics and prebiotic supplementation may be an effective alternative treatment for Candida infections.

In vitro analysis of postbiotic antimicrobial activity against Candida Species in a minimal synthetic model simulating the gut mycobiota in obesity.

Gut fungal imbalances, particularly increased Candida spp., are linked to obesity. This study explored the potential of Lactiplantibacillus plantarum cell-free extracts (postbiotics) to modulate the growth of Candida albicans and Candida kefyr, key members of the gut mycobiota. A minimal synthetic gut model was employed to evaluate the effects of Lactiplantibacillus plantarum postbiotics on fungal growth in mono- and mixed cultures. Microreactors were employed for culturing, fungal growth was quantified using CFU counting, and regression analysis was used to evaluate the effects of postbiotics on fungal growth. Postbiotics at a concentration of 12.5% significantly reduced the growth of both Candida species. At 24 h, both C. albicans and C. kefyr in monocultures exhibited a decrease in growth of 0.11 log CFU/mL. In contrast, mixed cultures showed a more pronounced antifungal effect, with C. albicans and C. kefyr reductions of 0.62 log CFU/mL and 0.64 log CFU/mL, respectively. Regression analysis using the Gompertz model supported the antifungal activity of postbiotics and revealed species-specific differences in growth parameters. These findings suggest that L. plantarum postbiotics have the potential to modulate the gut mycobiota by reducing Candida growth, potentially offering a therapeutic approach for combating fungal overgrowth associated with obesity.

Antifungal activity of propafenone on Candida spp. strains: interaction with antifungals and possible mechanism of action.

Introduction. The development of new antifungal drugs has become a global priority, given the increasing cases of fungal diseases together with the rising resistance to available antifungal drugs. In this scenario, drug repositioning has emerged as an alternative for such development, with advantages such as reduced research time and costs.Gap statement. Propafenone is an antiarrhythmic drug whose antifungal activity is poorly described, being a good candidate for further study.Aim. This study aims to evaluate propafenone activity against different species of Candida spp. to evaluate its combination with standard antifungals, as well as its possible action mechanism.Methodology. To this end, we carried out tests against strains of Candida albicans, Candida auris, Candida parapsilosis, Candida tropicalis, Candida glabrata and Candida krusei based on the evaluation of the MIC, minimum fungicidal concentration and tolerance level, along with checkerboard and flow cytometry tests with clinical strains and cell structure analysis by scanning electron microscopy (SEM).Results. The results showed that propafenone has a 50% MIC ranging from 32 to 256 µg ml-1, with fungicidal activity and positive interactions with itraconazole in 83.3% of the strains evaluated. The effects of the treatments observed by SEM were extensive damage to the cell structure, while flow cytometry revealed the apoptotic potential of propafenone against Candida spp.Conclusion. Taken together, these results indicate that propafenone has the potential for repositioning as an antifungal drug.

Differential adaptation of the yeast Candida anglica to fermented food.

A single strain of Candida anglica, isolated from cider, is available in international yeast collections. We present here seven new strains isolated from French PDO cheeses. For one of the cheese strains, we achieved a high-quality genome assembly of 13.7 Mb with eight near-complete telomere-to-telomere chromosomes. The genomes of two additional cheese strains and of the cider strain were also assembled and annotated, resulting in a core genome of 5966 coding sequences. Phylogenetic analysis showed that the seven cheese strains clustered together, away from the cider strain. Mating-type locus analysis revealed the presence of a MATa locus in the cider strain but a MATalpha locus in all cheese strains. The presence of LINE retrotransposons at identical genome position in the cheese strains, and two different karyotypic profiles resulting from chromosomal rearrangements were observed. Together, these findings are consistent with clonal propagation of the cheese strains. Phenotypic trait variations were observed within the cheese population under stress conditions whereas the cider strain was found to have a much greater capacity for growth in all conditions tested.

Cultivation of yeasts on liquid digestate to remove organic pollutants and nutrients and for potential application as co-culture with microalgae.

In this study, the growth of yeast and yeast-like fungi in the liquid digestate from vegetable wastes was investigated in order to remove nutrients and organic pollutants, and for their application as co-culture members with green microalgae. The studied yeast strains were characterized for their assimilative and enzymatic profiles as well as temperature requirements. In the first experimental stage, the growth dynamics of each strain were determined, allowing to select the best yeasts for further studies. In the subsequent stage, the ability of selectants to remove organic pollutants was assessed. Different cultivation media containing respectively 1:3, 1:1, 3:1 vol ratio of liquid digestate and the basal minimal medium were used. Among all tested yeast strains, Rhodotorula mucilaginosa DSM 70825 showed the most promising results, demonstrating the highest potential for removing organic substrates and nutrients. Depending on the medium, this strain achieved 50-80% sCOD, 45-60% tVFAs, 21-45% TN, 33-52% PO43- reduction rates. Similar results were obtained for the strain Candida sp. OR687571. The high nutrient and organics removal efficiency by these yeasts could likely be linked to their ability to assimilate xylose (being the main source of carbon in the liquid digestate). In culture media containing liquid digestate, both yeast strains achieved good viability and proliferation potential. In the liquid digestate medium, R. mucilaginosa and Candida sp. showed vitality at the level of 51.5% and 45.0%, respectively. These strains seem to be a good starting material for developing effective digestate treatment strategies involving monocultures and/or consortia with other yeasts or green microalgae.

Syzygium aromaticum essential oil and its major constituents: Assessment of activity against Candida spp. and toxicity.

Syzigium aromaticum essential oil (EO), eugenol, and ß-caryophyllene were evaluated regarding antifungal, antibiofilm, and in vitro toxicity. Additionally, in vivo toxicity of EO was observed. Anti-Candida activity was assessed through broth microdilution assay for all compounds. Time-kill assay (0, 1, 10, 30 min, 1, 2, and 4 h) was used to determine the influence of EO and eugenol on Candida Growth kinetics. Thereafter, both compounds were evaluated regarding their capacity to act on a biofilm formation and on mature biofilm, based on CFU/ml/g of dry weight. Cell Titer Blue Viability Assay was used for in vitro cytotoxicity, using oral epithelial cells (TR146) and human monocytes (THP-1). Lastly, Galleria mellonella model defined the EO in vivo acute toxicity. All compounds, except ß-cariofilene (MIC > 8000 µg/ml), presented antifungal activity against Candida strains (MIC 500-1000 µg/ml). The growth kinetics of Candida was affected by the EO (5xMIC 30 min onward; 10xMIC 10 min onward) and eugenol (5xMIC 10 min onward; 10xMIC 1 min onward). Fungal viability was also affected by 5xMIC and 10xMIC of both compounds during biofilm formation and upon mature biofilms. LD50 was defined for TR146 and THP1 cells at, respectively, 59.37 and 79.54 µg/ml for the EO and 55.35 and 84.16 µg/ml for eugenol. No sign of toxicity was seen in vivo up to 10mg/ml (20 x MIC) for the EO. S. aromaticum and eugenol presented antifungal and antibiofilm activity, with action on cell growth kinetics. In vivo acute toxicity showed a safe parameter for the EO up to 10 mg/ml.

Ability of Helicobacter pylori to internalize into Candida.

The following are our views regarding the "letter to the editor" (Helicobacter is preserved in yeast vacuoles! Does Koch's postulates confirm it?) by Alipour and Gaeini, and the response "letter to the editor" (Candida accommodates non-culturable Helicobacter pylori in its vacuole-Koch's postulates aren't applicable) by Siavoshi and Saniee. Alipour and Gaeini rejected the methods, results, discussion, and conclusions summarized in a review article by Siavoshi and Saniee. The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori (H. pylori) to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse, transporting potentially infectious H. pylori into the stomach of humans.

Understanding the mechanism of action of protease inhibitors in controlling the growth of the Candida Genus: potential candidates for development of new antifungal molecules.

There is a growing imperative for research into alternative compounds for the treatment of the fungal infections. Thus, many studies have focused on the analysis of antifungal proteins and peptides from different plant sources. Among these molecules are protease inhibitors (PIs). Previously, PIs present in the peptide-rich fractions called PEF1, PEF2 and PEF3 were identified from Capsicum chinense seeds, which have strong activity against phytopathogenic fungi. The aim of this study was to evaluate the mechanism of action and antimicrobial activity of PIs from PEF2 and PEF3 on the growth of yeasts of the genus Candida. In this work, analyses of their antimicrobial activity and cell viability were carried out. Subsequently, the mechanism of action by which the PIs cause the death of the yeasts was evaluated. Cytotoxicity was assessed in vitro by erythrocytes lysis and in vivo in Galleria mellonella larvae. PEF2 and PEF3 caused 100% of the growth inhibition of C. tropicalis and C. buinensis. For C. albicans inhibition was approximately 60% for both fractions. The PEF2 and PEF3 caused a reduction in mitochondrial functionality of 54% and 46% for C. albicans, 26% and 30% for C. tropicalis, and 71% and 68% for C. buinensis, respectively. These fractions induced morphological alterations, led to membrane permeabilization, elevated ROS levels, and resulted in necrotic cell death in C. tropicalis, whilst demonstrating low toxicity toward host cells. From the results obtained here, we intend to contribute to the understanding of the action of PIs in the control of fungal diseases of medical importance.

Hemolymph metabolism of black soldier fly (Diptera: Stratiomyidae), response to different supplemental fungi.

The black soldier fly, Hermetia illucens L. (Diptera: Stratiomyidae), is commonly used for organic waste recycling and animal feed production. However, the often inadequate nutrients in organic waste necessitate nutritional enhancement of black soldier fly larvae, e.g., by fungal supplementation of its diet. We investigated the amino acid composition of two fungi, Candida tropicalis (Castell.) Berkhout (Saccharomycetales: Saccharomycetaceae) and Pichia kudriavzevii Boidin, Pignal & Besson (Saccharomycetales: Pichiaceae), from the black soldier fly gut, and commercial baker's yeast, Saccharomyces cerevisiae Meyen ex E.C. Hansen (Saccharomycetales: Saccharomycetaceae), and their effects on larval growth and hemolymph metabolites in fifth-instar black soldier fly larvae. Liquid chromatography-mass spectrometry was used to study the effect of fungal metabolites on black soldier fly larval metabolism. Amino acid analysis revealed significant variation among the fungi. Fungal supplementation led to increased larval body mass and differential metabolite accumulation. The three fungal species caused distinct metabolic changes, with each over-accumulating and down-accumulating various metabolites. We identified significant alteration of histidine metabolism, aminoacyl-tRNA biosynthesis, and glycerophospholipid metabolism in BSF larvae treated with C. tropicalis. Treatment with P. kudriavzevii affected histidine metabolism and citrate cycle metabolites, while both P. kudriavzevii and S. cerevisiae treatments impacted tyrosine metabolism. Treatment with S. cerevisiae resulted in down-accumulation of metabolites related to glycine, serine, and threonine metabolism. This study suggests that adding fungi to the larval diet significantly affects black soldier fly larval metabolomics. Further research is needed to understand how individual amino acids and their metabolites contributed by fungi affect black soldier fly larval physiology, growth, and development, to elucidate the interaction between fungal nutrients and black soldier fly physiology.

Photoactivated riboflavin inhibits planktonic and biofilm growth of Candida albicans and non-albicans Candida species.

Fungal infections caused by Candida species pose a serious threat to humankind. Antibiotics abuse and the ability of Candida species to form biofilm have escalated the emergence of drug resistance in clinical settings and hence, rendered it more difficult to treat Candida-related diseases. Lethal effects of Candida infection are often due to inefficacy of antimicrobial treatments and failure of host immune response to clear infections. Previous studies have shown that a combination of riboflavin with UVA (riboflavin/UVA) light demonstrate candidacidal activity albeit its mechanism of actions remain elusive. Thus, this study sought to investigate antifungal and antibiofilm properties by combining riboflavin with UVA against Candida albicans and non-albicans Candida species. The MIC20 for the fluconazole and riboflavin/UVA against the Candida species tested was within the range of 0.125-2 µg/mL while the SMIC50 was 32 µg/mL. Present findings indicate that the inhibitory activities exerted by riboflavin/UVA towards planktonic cells are slightly less effective as compared to controls. However, the efficacy of the combination towards Candida species biofilms showed otherwise. Inhibitory effects exerted by riboflavin/UVA towards most of the tested Candida species biofilms points towards a variation in mode of action that could make it an ideal alternative therapeutic for biofilm-related infections.

Bioprospecting of Microalgae Isolated from the Adriatic Sea: Characterization of Biomass, Pigment, Lipid and Fatty Acid Composition, and Antioxidant and Antimicrobial Activity.

Marine microalgae and cyanobacteria are sources of diverse bioactive compounds with potential biotechnological applications in food, feed, nutraceutical, pharmaceutical, cosmetic and biofuel industries. In this study, five microalgae, Nitzschia sp. S5, Nanofrustulum shiloi D1, Picochlorum sp. D3, Tetraselmis sp. Z3 and Tetraselmis sp. C6, and the cyanobacterium Euhalothece sp. C1 were isolated from the Adriatic Sea and characterized regarding their growth kinetics, biomass composition and specific products content (fatty acids, pigments, antioxidants, neutral and polar lipids). The strain Picochlorum sp. D3, showing the highest specific growth rate (0.009 h-1), had biomass productivity of 33.98 ± 0.02 mg L-1 day-1. Proteins were the most abundant macromolecule in the biomass (32.83-57.94%, g g-1). Nanofrustulum shiloi D1 contained significant amounts of neutral lipids (68.36%), while the biomass of Picochlorum sp. D3, Tetraselmis sp. Z3, Tetraselmis sp. C6 and Euhalothece sp. C1 was rich in glycolipids and phospholipids (75%). The lipids of all studied microalgae predominantly contained unsaturated fatty acids. Carotenoids were the most abundant pigments with the highest content of lutein and neoxanthin in representatives of Chlorophyta and fucoxanthin in strains belonging to the Bacillariophyta. All microalgal extracts showed antioxidant activity and antimicrobial activity against Gram-negative E. coli and S. typhimurium and Gram-positive S. aureus.

Using HPLC-DAD and GC-MS Analysis Isolation and Identification of Anticandida Compounds from Gui Zhen Cao Herbs (Genus Bidens): An Important Chinese Medicinal Formulation.

Gui Zhen Cao is an herbal formulation that has been documented in Chinese traditional medicine as a remedy for diarrhea, dysentery, inflammation, and toxicity. The sources of this formulation (Bidens pilosa L., Bidens biternata (Lour.) Merr. & Sherff, Bidens bipinnata L.) are also listed in ethnomedicinal reports all over the world. In this study, all these plants are tested for in vitro anticandida activity. A quantitative evaluation of the phytochemicals in all these plants indicated that their vegetative parts are rich in tannins, saponins, oxalates, cyanogenic glycoside and lipids; moreover, the roots have high percentages of alkaloids, flavonoids, and phenols. The results indicated significant anticandida activity, especially for the hexane extract of B. bipinnata leaves which inhibited C. albicans (42.54%), C. glabrata (46.98%), C. tropicalis (50.89%), C. krusei (40.56%), and C. orthopsilosis (50.24%). The extract was subjected to silica gel chromatography and 220 fractions were obtained. Purification by High Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD) and Gas Chromatography tandem Mass Spectrometry (GC-MS/MS) analysis led to the identification of two anticandida compounds: dehydroabietic and linoleic acid having an inhibition of 85 and 92%, respectively.

Attempts to Access a Series of Pyrazoles Lead to New Hydrazones with Antifungal Potential against Candida species including Azole-Resistant Strains.

The treatment of benzylidenemalononitriles with phenylhydrazines in refluxing ethanol did not provide pyrazole derivatives, but instead furnished hydrazones. The structure of hydrazones was secured by X-ray analysis. The chemical proof was also obtained by direct reaction of 3,4,5-trimethoxybenzaldehyde with 2,4-dichlorophenylhydrazine. Newly synthesized hydrazones were tested against eight Candida spp. strains in a dose response assay to determine the minimum inhibitory concentration (MIC99). Five compounds were identified as promising antifungal agents against Candida spp. (C. albicans SC5314, C. glabrata, C. tropicalis, C. parapsilosis and C. glabrata (R azoles)), with MIC99 values ranging from 16 to 32 µg/mL and selective antifungal activity over cytotoxicity.

In vitro activities of carvacrol, cinnamaldehyde and thymol against Candida biofilms.

Oral candidiasis is frequently associated with Candida biofilms. Biofilms are microbial communities related to persistent, recalcitrant and difficult to-treat infections. Conventional treatments are not sufficient to overcome biofilm-associated candidiasis; thus, the search of new antifungal compounds is necessary. In the current study, we have evaluated the effect of three phytocompounds, carvacrol, cinnamaldehyde and thymol, against Candida planktonic and sessile cells. Reduction in biofilm biomass and metabolic activity was assessed during adhesion and mature biofilm phases. Candida albicans was the most biofilm-producing Candida species. All phytocompounds tested were fungicidal against Candida planktonic cells. Cinnamaldehyde was the most active in inhibiting biofilm adhesion, but carvacrol and thymol significantly reduced both mature biofilm biomass and metabolic activity. These results highlight the role of cinnamaldehyde, carvacrol and thymol as promising alternatives for the treatment of candidiasis due to their antibiofilm capacities, and stress the necessity to continue studies on their safety, toxicity and pharmacodynamics and pharmacokinetics.

Novel Antifungal Activity of Q-Griffithsin, a Broad-Spectrum Antiviral Lectin.

There is a rising global incidence of Candida strains with high levels of resistance to fluconazole and other antifungal drugs, hence the need for novel antifungal treatment strategies. Here, we describe the first evidence of antifungal activity of Q-Griffithsin (Q-GRFT), a recombinant oxidation-resistant variant of Griffithsin, a marine red algal lectin with broad-spectrum antiviral activity. We demonstrated that Q-GRFT binds to α-mannan in the Candida albicans cell wall. We also observed that Q-GRFT binding disrupted cell wall integrity and induced reactive oxidative species (ROS) formation, resulting in cell death. Furthermore, we showed that Q-GRFT inhibited the growth of other Candida species C. glabrata, C. parapsilosis, and C. krusei and had modest activity against some strains of multi- and pandrug-resistant C. auris. We found that Q-GRFT induced differential expression of numerous genes involved in response to cell stress, including those responsible for neutralizing ROS production and cell cycle regulation. In conclusion, this novel antifungal activity suggests that Q-GRFT is potentially an ideal drug candidate and represents an alternative strategy for the prevention and treatment of candidiasis. IMPORTANCE Fungal infections contribute to morbidity and mortality annually, and the number of organisms that are nonresponsive to the current available drug regimens are on the rise. There is a need to develop new agents to counter these infections and to add to the limited arsenal available to treat fungal infections. Our study has identified Q-GRFT, a broad-spectrum antiviral protein that harbors growth-inhibitory activity against several Candida strains, as a potential candidate for the prevention and treatment of fungal infections.

A Natural Alternative Treatment for Urinary Tract Infections: Itxasol©, the Importance of the Formulation.

Genito-urinary tract infections have a high incidence in the general population, being more prevalent among women than men. These diseases are usually treated with antibiotics, but very frequently, they are recurrent and lead to the creation of resistance and are associated with increased morbidity and mortality. For this reason, it is necessary to develop new compounds for their treatment. In this work, our objective is to review the characteristics of the compounds of a new formulation called Itxasol© that is prescribed as an adjuvant for the treatment of UTIs and composed of ß-arbutin, umbelliferon and n-acetyl cysteine. This formulation, based on biomimetic principles, makes Itxasol© a broad-spectrum antibiotic with bactericidal, bacteriostatic and antifungal properties that is capable of destroying the biofilm and stopping its formation. It also acts as an anti-inflammatory agent, without the adverse effects associated with the recurrent use of antibiotics that leads to renal nephrotoxicity and other side effects. All these characteristics make Itxasol© an ideal candidate for the treatment of UTIs since it behaves like an antibiotic and with better characteristics than other adjuvants, such as D-mannose and cranberry extracts.

Fungal species in endodontic infections: A systematic review and meta-analysis.

Fungal infections are common on oral mucosae, but their role in other oral sites is ill defined. Over the last few decades, numerous studies have reported the presence of fungi, particularly Candida species in endodontic infections, albeit in relatively small numbers in comparison to its predominant anaerobic bacteriome. Here, we review the fungal biome of primary and secondary endodontic infections, with particular reference to the prevalence and behavior of Candida species. Meta-analysis of the available data from a total of 39 studies fitting the inclusion criteria, indicate the overall weighted mean prevalence (WMP) of fungal species in endodontic infections to be 9.11% (from a cumulative total of 2003 samples), with 9.0% in primary (n = 1341), and 9.3% in secondary infections (n = 662). Nevertheless, WMP for fungi in primary and secondary infections which were 6.3% and 7.5% for culture-based studies, increased to 12.5% and 16.0% in molecular studies, respectively. The most prevalent fungal species was Candida spp. The high heterogeneity in the reported fungal prevalence suggests the need for standardized sampling, and speciation methods. The advent of the new molecular biological analytical platforms, such as the next generation sequencing (NGS), and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF), that enables identification and quantitation of a broad spectrum of hitherto unknown organisms in endodontic infections should radically alter our understanding of the endodontic mycobiome in the future. Candida spp. appear to be co-pathogens with bacteria in approximately one in ten patients with endodontic infections. Hence, clinicians should comprehend the importance and the role of fungi in endodontic infections and be cognizant of the need to eradicate both bacteria and fungi for successful therapy.