Biofilm matrix regulation by Candida glabrata Zap1 under acidic conditions: transcriptomic and proteomic analyses.

The vaginal acidic environment potentiates the formation of Candida glabrata biofilms, leading to complicated and recurrent infections. Importantly, the production of matrix is known to contribute to the recalcitrant features of Candida biofilms. In this study, we reveal that Zap1 regulates the matrix of C. glabrata acidic biofilms and analyzed the modulation of their transcriptome (by microarrays) and matrix proteome (by LC-MS/MS) by Zap1. For that, the deletion mutant zap1Δ and its complemented strain zap1Δ::ZAP1 were constructed, and their biofilms were developed at pH 4 (adjusted with lactic acid). The results revealed that Zap1 is a negative regulator of the total amount of protein and carbohydrate in the biofilm matrix. Accordingly, various genes and matrix proteins with predicted functions in the regulation of carbohydrate metabolism, sugar binding, sugar transport, and adhesion (including Epa family) were repressed by Zap1. Nevertheless, the results also suggested that Zap1 is essential to the delivery and organization of some matrix components. Indeed, Zap1 was required for the secretion of 122 proteins to the matrix and induced the expression of 557 genes, including various targets involved in glucan metabolism. Additionally, Zap1 induced targets with roles in virulence, resistance to antifungals, and host immunity evasion, including yapsins, ERG family, and moonlighting proteins. Zap1 was also required for the secretion of acidic-specific matrix proteins, indicating a contribution to the response to the acidic environment. Overall, this study demonstrates that Zap1 is a relevant regulator of the biofilm matrix, contributing to a better understanding of C. glabrata acidic biofilms.IMPORTANCEThe rising prevalence of vulvovaginal candidiasis (VVC) and the increasing presence of Candida spp. with aggressive virulence features and low susceptibility to common antifungals, particularly Candida glabrata, have resulted in more severe, prolonged, and recurrent cases of VVC, with significant implications for patients. This research offers valuable insights into the molecular changes that contribute to the formation of C. glabrata biofilms in the acidic vaginal environment, representing a significant advancement in the understanding of C. glabrata's virulence. Notably, this study identified Zap1 as a critical regulator of C. glabrata biofilm matrix, with additional potential roles in adhesion, antifungal resistance, evasion of host immunity, and response to acidic conditions, making it a promising target for new therapeutic approaches. Importantly, Zap1 is the first regulator of the biofilm matrix to be identified in C. glabrata, and the elucidation of its targets (including genes and matrix proteins) lays a strong foundation for future research.

The first prevalence and antifungal susceptibility profile of Candida infections in Palestine, 2022.

BACKGROUND: Candida spp. are the most common cause of opportunistic fungal infections and are associated with a high mortality rate worldwide. In Palestine, the prevalence of Candida spp. infections remains elusive. METHODS: We performed our study at two hospitals in Palestine (Istishari Arab Hospital, and Najah National University Hospital). All patients diagnosed with candidiasis during the year 2022 have participated in the study. The prevalence of Candida spp., their distribution, and the activity of selected antifungals against Candida pathogens were assessed. In combination with phenotypic properties, Candida isolates were identified and tested for antifungal susceptibility using the colorimetric VITEK-2 Compact system. RESULTS: Our results showed that the prevalence of Candida spp. among infected samples was 11.6%. A total of eleven different Candida spp. were identified. Among these isolates, C. albicans (46.54%) was the most frequent, followed by C. glabrata (16.14%), C. tropicalis (13.83%), C. parapsilosis (4.82%), C. krusei (3.56%), C. dubliniensis (2.09%), C. ciferrii (1.67%), C. lusitaniae (0.83%), C. guilliermondii (0.62%), C. kefyer (0.41%) and C. spherica (0.20%). Among C. albicans, all isolates were 100% susceptible to fluconazole and micafungin. The susceptibility rates to Amphotericin B and flucytosine were 95% and 99%, respectively. The susceptibility rates of non-albicans Candida spp. (NAC) to fluconazole, voriconazole, amphotericine B, caspofungin, flucytosine and micafungin were 70%, 99%, 97%, ,72%, 92% and 100%, respectively. The incidence of Candida infections was higher in the intensive care unit and surgery department as compared to other hospital departments. CONCLUSIONS: Four pathogens are responsible for the most invasive infections: C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis. A notable characteristic of this study was the high frequency of NAC species which were often more resistant to antifungal agents. A quick and accurate system like Vitek 2 compact was suggested for the careful species identification of clinical isolates of Candida. We suggest that continued surveillance of species distribution and susceptibility to antifungals will enhance future burden estimates and assist in evaluating preventative measures' effectiveness.

Antifungal Susceptibility Data and Epidemiological Distribution of Candida spp.: An In Vitro Five-Year Evaluation at University Hospital Policlinico of Catania and a Comprehensive Literature Review.

BACKGROUND: Invasive fungal infections represent a concerning healthcare issue, with Candida spp. reported as the main aetiological agent. Candida spp. bloodstream infections show high mortality rates, indicating increasing antifungal-resistance episodes as a contributing feature. Despite the global prevalence of C. albicans, non-albicans species emerged as significant in the last decades. METHODS: The present manuscript reports a five-year evaluation on Candida spp. bloodstream isolates and their antifungal susceptibility profiles, aiming to enrich the literature and epidemiological data. RESULTS: According to the gathered data, antifungal-resistance cases remained uncommon. However, the study revealed rare resistance phenotypes such as a single case of pan-echinocandin resistance C. albicans. CONCLUSIONS: Finally, a comprehensive review of Candida spp. antifungal resistance integrates the data, emphasizing the extreme species-specific variability and the consequent importance of always providing species identification.

Azole Combinations and Multi-Targeting Drugs That Synergistically Inhibit Candidozyma auris.

Limited antifungal treatment options and drug resistance require innovative approaches to effectively combat fungal infections. Combination therapy is a promising strategy that addresses these pressing issues by concurrently targeting multiple cellular sites. The drug targets usually selected for combination therapy are from different cellular pathways with the goals of increasing treatment options and reducing development of resistance. However, some circumstances can prevent the implementation of combination therapy in clinical practice. These could include the increased risk of adverse effects, drug interactions, and even the promotion of drug resistance. Furthermore, robust clinical evidence supporting the superiority of combination therapy over monotherapy is limited and underscores the need for further research. Despite these challenges, synergies detected with different antifungal classes, such as the azoles and echinocandins, suggest that treatment strategies can be optimized by better understanding the underlying mechanisms. This review provides an overview of multi-targeting combination strategies with a primary focus on Candidozyma auris infections.

Invasive candidiasis in a pediatric tertiary hospital: Epidemiology, antifungal susceptibility, and mortality rates.

Invasive infections caused by non-albicans Candida are increasing worldwide. However, there is still a lack of information on invasive candidiasis (IC) in the pediatric setting, including susceptibility profiles and clonal studies. We investigated the clinical, epidemiologic, and laboratory characteristics of IC, possible changes in antifungal susceptibility profiles over time, and the occurrence of clonality in our tertiary children's hospital. We analyzed 123 non-duplicate Candida isolates from sterile sites of pediatric patients in a tertiary hospital in southern Brazil, between 2016 and 2021. Data on demographics, comorbidities, and clinical outcomes were collected. Candida species distribution, antifungal susceptibility profiles, biofilm production, and molecular epidemiology of isolates were assessed using reference methods. The range of IC incidence was 0.88-1.55 cases/1000 hospitalized patients/year, and the IC-related mortality rate was 20.3%. Of the total IC cases, 42.3% were in patients aged < 13 months. Mechanical ventilation, parenteral nutrition, and intensive care unit (ICU) admission were common in this group. In addition, ICU admission was identified as a risk factor for IC-related mortality. The main site of Candida spp. isolation was blood, and non-albicans Candida species were predominant (70.8%). No significant clonal spread was observed among isolates of the three most commonly isolated species, and 99.1% of all isolates were biofilm producers. Non-albicans Candida species were predominant in this study. Notably, clonal expansion and emergence of antifungal drug resistance were not observed in our pediatric setting.

The epidemiology of invasive candidiasis has changed over time and there is still a lack of information in the pediatric setting. Non-albicans Candida species predominated in this study, clonal expansion and emergence of antifungal drug resistance were not observed in our pediatric setting.

Antifungal efficacy of photodynamic therapy on Cryptococcus and Candida species is enhanced by Streptomyces spp. extracts in vitro.

The research on actinobacteria isolated from traditional medicinal plants is limited. Here, four new Streptomyces isolates (Ha1, Pp1, UzK and UzM) were obtained from the rhizospheres of Helianthus annuus, Pongamia pinnata and Ziziphus mauritiana, frequently utilized in Indian traditional medicine. The Streptomyces isolates aqueous extracts were studied alone against the growth of the Cryptococcus neoformans H99 reference strain, the fluconazole-tolerant T1-5796 and 89-610 strains, three histone deacetylase (HDAC) genes mutant strains, C. gattii NIH198, Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis to determine minimum inhibitory concentration (MIC). Next, the extracts were employed in combination with aluminium-phthalocyanine chloride nanoemulsion-mediated photodynamic therapy to evaluate a possible interaction. We demonstrated that the C. neoformans T1-5796 fluconazole-tolerant strain was more severely inhibited by the Pp1 isolate extract (MIC: 6 mg mL-1) than H99, which was not inhibited. Growth inhibition of the HDAC null mutants was more prominent for the extract of the UzM isolate, showing inhibition at 2 mg mL-1. The UzM extract was also the most effective in hindering the Candida species proliferation, with MIC values ranging from 10 to 40 mg mL-1. The four Streptomyces extracts, especially UzK and UzM, significantly enhanced the antifungal effect of the photodynamic therapy. Our results indicate these Streptomyces isolates as sources of novel metabolites which could potentiate the effect of photodynamic therapy in controlling yeasts superficial infections.

Prevalence of Trichomoniasis and Vulvovaginal Candidiasis among Married Women in Duhok City, Kurdistan Region, Iraq.

Trichomonas vaginalis and Candida spp. are the most common causes of vaginal infections among reproductive-age women. T. vaginalis is a sexual protozoa parasite that causes trichomoniasis. Candida spp. are fungal and cause infection in the female genital tract named candidiasis. Both microorganisms if not treated correctly may lead to various complications, such as abortion, premature delivery, disorders of menstrual cycle, and infertility. The current study aimed to study the frequency of infections with T. vaginalis and Candida spp., including C. albicans, C. krusei, and C. glabrata, among females with vaginal infection in Duhok City, Kurdistan region, Iraq. A total of 400 vaginal swabs were collected from women with vaginal infections that attended the Vin Private Laboratory (n=250) and Arveen Private Laboratory (n=150). Out of these 400 vaginal swabs samples, 24 samples were recorded positive for T. vaginalis by direct smear and 100 samples for candidiasis by culturing on the CHROMagarTM Candida. Three species of Candida were isolated, namely C. albicans, C. krusei, and C. glabrata, and their prevalence rates were obtained at 60.9%., 28.25, 7.3%, and 3.6%, respectively. Vaginal infection was commonly found in the age group of 25-35 years (49.6%), followed by the age group of 35-45 years (36.4%). Moreover, 3.2% of samples were found to have a mixed infection with trichomoniasis and candidiasis. Because these two causative agents cause numerous complications in women, it is highly recommended proper controlling measures, such as health education, personal hygiene, and treatment of infected women, be implemented to prevent or decrease vaginal infection.

Improving antifungal lipid-based drug delivery against Candida: a review.

INTRODUCTION: Fungal infections, particularly those caused by Candida spp. have increased in recent years. A primary contributor to this surge was the COVID-19 pandemic, where many hospitalized patients had secondary fungal infections. Additionally, the emergence of resistant and multi-resistant fungal strains has become increasingly problematic due to the limited therapeutic options available in antifungal treatments. AREAS COVERED: This review presents a comprehensive analysis of recent studies focused on the development and characterization of lipid-based nanosystems as an emerging and promising therapeutic alternative. These systems have been evaluated for their potential to deliver antifungal agents specifically targeting resistant Candida spp. strains, offering a controlled and sustained release of drugs. EXPERT OPINION: Lipid-based nanomaterials are promising tools for the controlled and sustained release of drugs, particularly in treating Candida spp. infections. Although substantial research has been dedicated to development of these nanomaterials, only a few have reached clinical application, such as liposomal amphotericin B, for example. Therefore, it is critical to push forward with advancements to bring these nanomedicines into clinical practice, where they can contribute meaningfully to mitigating the challenge of resistant and lethal fungal strains.

Elucidation of the mechanisms of fluconazole resistance and repurposing treatment options against urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt.

BACKGROUND: The incidence of fungal urinary tract infections (UTIs) has dramatically increased in the past decades, with Candida arising as the predominant etiological agent. Managing these infections poses a serious challenge to clinicians, especially with the emergence of fluconazole-resistant (FLC-R) Candida species. In this study, we aimed to determine the mechanisms of fluconazole resistance in urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt, assess the correlation between fluconazole resistance and virulence, and explore potential treatment options for UTIs caused by FLC-R Candida strains. RESULTS: Fluconazole susceptibility testing of 34 urinary Candida isolates indicated that 76.5% were FLC-R, with a higher prevalence of resistance recorded in non-albicans Candida spp. (88.9%) than in Candida albicans (62.5%). The calculated Spearman's correlation coefficients implied significant positive correlations between fluconazole minimum inhibitory concentrations and both biofilm formation and phospholipase production. Real-time PCR results revealed that most FLC-R isolates (60%) significantly overexpressed at least one efflux pump gene, while 42.3% significantly upregulated the ERG11 gene. The most prevalent mutation detected upon ERG11 sequencing was G464S, which is conclusively linked to fluconazole resistance. The five repurposed agents: amikacin, colistin, dexamethasone, ketorolac, and sulfamethoxazole demonstrated variable fluconazole-sensitizing activities in vitro, with amikacin, dexamethasone, and colistin being the most effective. However, the fluconazole/colistin combination produced a notable reduction (49.1%) in bladder bioburden, a 50% decrease in the inflammatory response, and tripled the median survival span relative to the untreated murine models. CONCLUSIONS: The fluconazole/colistin combination offers a promising treatment option for UTIs caused by FLC-R Candida, providing an alternative to the high-cost, tedious process of novel antifungal drug discovery in the battle against antifungal resistance.

Evaluation of amlodipine against strains of Candida spp. in planktonic cells, developing biofilms and mature biofilms.

Aim: To evaluate the antifungal activity of amlodipine against strains of Candida spp. and to its possible mechanism of action.Methods: Broth microdilution tests were used to determine the minimum inhibitory concentration, while the synergistic activity was evaluated by calculating the fractional inhibitory concentration index. The action of amlodipine against biofilms was determined using the MTT assay and its possible mechanism of action was investigated through flow cytometry tests.Results: Amlodipine showed MICs ranging from 62.5 to 250 µg/ml, in addition to action against pre-formed and forming biofilms, with reductions between 50 and 90%. Amlodipine increases the externalization of phosphatidylserine and reduces the cell viability of fungal cells, suggesting apoptosis.Conclusion: Amlodipine had good antifungal activity against planktonic cells and biofilms of Candida spp., by leading the cells to apoptosis.

Candida is a type of fungus that can cause diseases. This fungus became stronger over time and drugs can no longer kill them easily, so it is important to find new drugs. We decided to study whether amlodipine, a drug used for heart disease, has action against Candida. We discovered that amlodipine make fungi weaker. We still need to do more studies to find out if amlodipine can help prevent Candida diseases.

Unraveling the complexities of antifungal susceptibility testing in Candida spp.: Insights from design of experiments.

Our study delved into the intricate dynamics of antifungal susceptibility testing for Candida spp., employing a Design of Experiments approach. We systematically investigated the influence of pH, temperature, inoculum size, and glucose concentration on both growth patterns and inhibitory concentrations of Candida spp. Our findings underscore the nuanced interplay between these factors, revealing significant impacts on susceptibility outcomes. Notably, even minor adjustments in these parameters yielded substantial variations in growth and inhibitory concentrations, underscoring the critical importance of meticulous control over growth conditions in antifungal susceptibility testing protocols. Each Candida isolates exhibited unique susceptibility profiles, necessitating tailored culture conditions for accurate testing. Our study sheds light on the variability inherent in Candida spp. growth patterns and emphasizes the need for standardized protocols to ensure consistency across laboratories. By leveraging the design of experiments, our research provides a systematic framework for unraveling the complexities of antifungal susceptibility testing, offering valuable insights for optimizing testing protocols and informing clinical decision-making in antifungal treatment. These findings represent a significant step towards enhancing the efficacy and reliability of antifungal susceptibility testing in clinical practice.

Anticandidal activity of Croton heliotropiifolius Kunth essential oil is enhanced by N-acetylcysteine and itraconazole.

Aim: Evaluate the anticandidal effect of Croton heliotropiifolius Kunth essential oil and its interaction with azoles and N-acetylcysteine (NAC) against planktonic cells and biofilms.Materials & methods: Broth microdilution and checkerboard methods were used to evaluate the individual and combined activity with fluconazole and itraconazole (ITRA). The antibiofilm effect of the oil was assessed in 96-well plates alone and combined with ITRA and NAC, and cytotoxicity determined by MTT.Results: The oil inhibited all Candida species growth. The activity was enhanced when associated with ITRA and NAC for planktonic cells and biofilms in formation. The effective concentrations were lower than the toxic ones to V79 cells.Conclusion: C. heliotropiifolius Kunth essential oil is an anticandidal alternative, and can be associated with ITRA and NAC.

Candida is a type of fungus that can cause disease in people. In recent years, the number of available drugs to treat this disease have declined. It is important to search for new drugs. Plants are often used to improve health, so we tested the essential oil of a plant called Croton heliotropiifolius to see if it could kill the fungus. We found that the essential oil could kill the fungus, and could be used with other drugs to improve their effects.

Prosthetic Joint Infections due to Candida Species: A Multicenter International Study.

BACKGROUND: Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI. METHODS: This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up. RESULTS: A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777). CONCLUSIONS: Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration.

Antifungal activity of tannic acid against Candida spp. and its mechanism of action.

The increase in fungal resistance is a major public health concern. In this context, Candida spp. is an important genus related to invasive diseases, especially in immunosuppressed patients. The relevance of alternative approaches to increasing fungal resistance stands out, in which products of natural origin demonstrate potential antifungal activity in vitro against Candida spp. In this sense, this work aimed to evaluate the in vitro activity of tannic acid against Candida spp. Minimum inhibitory concentration (MIC) was determined for tannic acid and the antifungals, and the checkerboard assay was performed to analyze the interactions between them. Furthermore, we evaluated the tannic acid antibiofilm activity and its possible mechanism of action. Tannic acid showed MIC ranging to 0.06 to 0.5 µg/ml and showed no loss of effectiveness when combined with antifungals. Also, is safe at the concentrations it exerts its antifungal activity in pre-formed biofilms, as demonstrated by IC50 in murine fibroblasts cells and the hemolytic assay. Additionally, its mechanisms of action can be related with induction of signals that lead to apoptosis in fungal cells.

Antimicrobial Activity of Olive Leaf Extract to Oral Candida Isolates.

OBJECTIVES: The aim of this study was to determine the antifungal activity of olive leaf extract (OLE) and the synergistic effect of standard antifungal therapy and OLE against clinical oral Candida species' isolates. MATERIALS AND METHOD: The susceptibility of 60 clinical isolates of the Candida species (36 C. albicans, 16 C. krusei, 5 C. glabrata and 3 C. tropicalis) was tested with four concentrations of OLE (60 µg/µL, 120 µg/µL, 240 µg/µL and 333 µg/µL) and the synergistic effect of standard antifungal therapy and OLE (miconazole (MIC) + 333 µg/µL OLE and nystatin (NYS) + 333 µg/µL OLE). The antimicrobial activity was tested using the disk diffusion method. RESULTS: All concentrations (60 µg/µL, 120 µg/µL, 240 µg/µL and 333 µg/µL) of OLE showed a statistically significant effect on all Candida species compared to the control (DMSO) except for the lowest concentration (60 µg/µL) tested on C. glabrata. There was a dose-dependent effect of OLE on tested samples. Concentrations of 240 µg/µL and 333 µg/µL showed statistically significant higher antifungal activity compared to the lowest concentration of 60 µg/µL. No statistically significant synergistic effect of OLE and standard antifungal therapy was found compared with standard therapy alone. CONCLUSIONS: The results of this study present the significant antimicrobial effect of OLE against all tested Candida species except for the lowest concentration on C. glabrata. Increasing the concentration of OLE also increases its effect on Candida species. This indicates the possible potential effect of OLE in the treatment of Candida-related oral diseases.

Anticandidal Properties of Launaea sarmentosa among the Salt Marsh Plants Collected from Palk Bay and the Gulf of Mannar Coast, Southeastern India.

Tidal wetlands, commonly known as salt marshes, are highly productive ecosystems in temperate regions worldwide. These environments constitute a unique flora composed primarily of salt-tolerant herbs, grasses, and shrubs. This study investigated the therapeutic properties of ten salt marsh plants collected mainly from Palk Bay and Mannar Gulf against Candida disease. This study examined the changes in natural plant products associated with their anti-Candida growth activity during two distinct seasonal changes-monsoon and summer. The potential of the salt marshes to inhibit the growth of five different Candida strains was assessed using four solvents. In phytochemical analysis, the extracts obtained from a Launaea sarmentosa exhibited the highest results compared to the other plant extracts. Fourier transform infrared spectroscopy revealed 12 peaks with alkane, aldehyde, amine, aromatic ester, phenol, secondary alcohol, and 1,2,3,4-tetrasubstituted. Gas-chromatography-mass spectrometry detected 30 compounds. Cyclotetracosane, lupeol, ß-amyrin, and 12-oleanen-3-yl acetate showed the highest peak range. In particular, plant samples collected during the monsoon season were more effective in preventing Canda growth than the summer plant samples. In the monsoon season, the salt marsh plant extracted with ethyl acetate showed a high anti-Candida growth activity, while in the summer, the acetone extract exhibited a higher anti-Candida growth activity than the other solvents. The hexane extract of L. sarmentosa showed the highest inhibition zone against all Candidal strains. Furthermore, compounds, such as ß-amyrin, lupeol, and oxirane, from the hexane extract of L. sarmentosa play a vital role in anti-Candida activity. This paper reports the potential of tidal marsh plant extracts for developing new antifungal agents for Candida infections.

Global Epidemiology of Invasive Infections by Uncommon Candida Species: A Systematic Review.

Emerging and uncommon Candida species have been reported as an increasing cause of invasive Candida infections (ICI). We aim to systematize the global epidemiology associated with emergent uncommon Candida species responsible for invasive infections in adult patients. A systematic review (from 1 January 2001 to 28 February 2023) regarding epidemiological, clinical, and microbiological data associated to invasive Candida infections by uncommon Candida spp. were collected. In total, 1567 publications were identified, and 36 were selected according to inclusion criteria (45 cases). The chosen studies covered: C. auris (n = 21), C. haemulonii (n = 6), C. fermentati (n = 4), C. kefyr (n = 4), C. norvegensis (n = 3), C. nivariensis (n = 3), C. bracarensis (n = 1), C. duobushaemulonii (n = 1), C. blankii (n = 1), and C. khanbhai (n = 1). Over the recent years, there has been an increase in the number of invasive infections caused by uncommon Candida spp. Asia and Europe are the continents with the most reported cases. The challenges in strain identification and antifungal susceptibility interpretation were significant. The absence of clinical breakpoints for the susceptibility profile determination for uncommon Candida spp. makes interpretation and treatment options a clinical challenge. It is crucial that we focus on new and accessible microbiology techniques to make fast and accurate diagnostics and treatments.

Molecular analysis of cutaneous yeast isolates in the mycobiota of children with atopic dermatitis.

The skin of patients with atopic dermatitis (AD) has a greater diversity of mycobiota. An observational, prospective, cross-sectional, analytical, and comparative study was conducted involving 80 patients with AD Group (ADG) and 50 individuals without AD (wADG) in a tertiary hospital in Brazil. Skin scale samples were collected from the frontal, cervical, fossae cubital, and popliteal regions and identified using molecular biology techniques. The results showed that 47.5% of ADG had identified yeasts compared to 0% of wADG (P < .001). The yeasts Rhodotorula mucilaginosa and Candida parapsilosis were the most abundant. The probability of colonization increased with age, showing values of 40% at 60 months and 80% at 220 months (P = .09). The cervical region (12.5%) was colonized to the greatest extent. Our findings revealed that positive mycology was not more probable when the scoring of atopic dermatitis or eczema area and severity index value increased (P = .23 and .53, respectively). The results showed that the sex, age, and different population types directly affected the composition of the mycobiota in the population analyzed. A higher frequency of colonization and greater diversity of yeast species were detected in the cutaneous mycobiota of children with AD.

Atopic dermatitis (AD) is a skin disease that can be colonized by microorganisms. We evaluated patients with and without the disease and found a higher frequency of colonization by Rhodotorula mucilaginosa and Candida parapsilosis on the skin of children with AD.

Analysis of the anti-Candida activity of tricyclic antidepressants in association with amphotericin B and their antifungal mechanisms.

Candida species are among the priority pathogens in the area of research and development. Due to the problems associated with resistance to antifungals, new therapeutic alternatives are necessary. In this regard, drug repositioning has gained prominence. The objective of this study was to evaluate the activity of three tricyclic antidepressants (TCAs) - amitriptyline (AMT), nortriptyline (NOR) and clomipramine (CLO) - isolated or associated with antifungals against strains of Candida spp., as well as to analyze the possible mechanism of action. Among the methods used were broth microdilution tests, tolerance level assessment, checkerboard assays, flow cytometry and fluorescence microscopy. Furthermore, Candida cells were visualized after treatments by scanning electron microscopy (SEM). AMT presented MIC 50% in the range of 16 to 128 µg/mL, NOR from 8 to 128 µg/mL, and CLO from 8 to 64 µg/mL, with all three TCAs having a fungicidal inhibitory action profile. For these TCAs, there was synergism with amphotericin B (AMB) in 100% of the isolates. In association with fluconazole (FLC) and itraconazole (ITR), there were mostly indifferent interactions. TCAs isolated and associated with AMB reduced cell viability, promoted DNA fragmentation and damage, caused mitochondrial depolarization, externalization of phosphatidylserine, produced reactive oxygen species (ROS), decreased reduced glutathione (GSH) and increased carbonyl protein levels, causing morphological changes. The results suggest the antifungal mechanism of the TCAs works via the apoptotic pathway.

Mangiferin potentiates the activity of antifungal agents against fluconazole-resistant Candida spp.

Aim: To evaluate the antifungal activity of mangiferin against Candida spp. resistant to fluconazole.Materials & methods: The antifungal activity of mangiferin was assessed using broth microdilution and its interaction with azoles and amphotericin B was evaluated by checkerboard. The activity of mangiferin against Candida spp. biofilms was assessed using the MTT colorimetric assay and its possible mechanism of action was evaluated using flow cytometry.Results: Mangiferin showed activity against Candida albicans, Candida tropicalis and Candida parapsilosis resistant to fluconazole and showed synergism with azoles and amphotericin B. Mangiferin increased the activity of antifungals against Candida biofilms and caused depolarization of the mitochondrial membrane and externalization of phosphatidylserine, suggesting apoptosis.Conclusion: mangiferin combined with antifungals has potential against Candida spp.

Candida is a type of fungus that can make people ill. Over time, many species of Candida have found ways to resist the drugs used to kill them. It is important to find new drugs. We decided to see if a substance called mangiferin works against Candida. We found that mangiferin works against Candida and may help other drugs to work better. We still need to do more studies to find out whether mangiferin can help prevent diseases caused by Candida in the future.