Outcomes by Candida spp. in the ReSTORE Phase 3 trial of rezafungin versus caspofungin for candidemia and/or invasive candidiasis.

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

Metabolic engineering of Candida tropicalis for efficient 1,2,4-butanetriol production.

1,2,4-Butanetriol serves as a precursor in the manufacture of diverse pharmaceuticals and the energetic plasticizer 1,2,4-butanetriol trinitrate. The study involved further modifications to an engineered Candida tropicalis strain, aimed at improving the production efficiency of 1,2,4-butanetriol. Faced with the issue of xylonate accumulation due to the low activity of heterologous xylonate dehydratase, we modulated iron metabolism at the transcriptional level to boost intracellular iron ion availability, thus enhancing the enzyme activity by 2.2-fold. Addressing the NADPH shortfall encountered during 1,2,4-butanetriol biosynthesis, we overexpressed pivotal genes in the NADPH regeneration pathway, achieving a 1,2,4-butanetriol yield of 3.2 g/L. The introduction of calcium carbonate to maintain pH balance led to an increased yield of 4 g/L, marking a 111% improvement over the baseline strain. Finally, the use of corncob hydrolysate as a substrate culminated in 1,2,4-butanetriol production of 3.42 g/L, thereby identifying a novel host for the conversion of corncob hydrolysate to 1,2,4-butanetriol.

Genetic modification of Candida maltosa, a non-pathogenic CTG species, reveals EFG1 function.

Candida maltosa is closely related to important pathogenic Candida species, especially C. tropicalis and C. albicans, but it has been rarely isolated from humans. For this reason, through comparative studies, it could be a powerful model to understand the genetic underpinnings of the pathogenicity of Candida species. Here, we generated a cohesive assembly of the C. maltosa genome and developed genetic engineering tools that will facilitate studying this species at a molecular level. We used a combination of short and long-read sequencing to build a polished genomic draft composed of 14 Mbp, 45 contigs and close to 5700 genes. This assembly represents a substantial improvement from the currently available sequences that are composed of thousands of contigs. Genomic comparison with C. albicans and C. tropicalis revealed a substantial reduction in the total number of genes in C. maltosa. However, gene loss seems not to be associated to the avirulence of this species given that most genes that have been previously associated with pathogenicity were also present in C. maltosa. To be able to edit the genome of C. maltosa we generated a set of triple auxotrophic strains so that gene deletions can be performed similarly to what has been routinely done in pathogenic Candida species. As a proof of concept, we generated gene knockouts of EFG1, a gene that encodes a transcription factor that is essential for filamentation and biofilm formation in C. albicans and C. tropicalis. Characterization of these mutants showed that Efg1 also plays a role in biofilm formation and filamentous growth in C. maltosa, but it seems to be a repressor of filamentation in this species. The genome assembly and auxotrophic mutants developed here are a key step forward to start using C. maltosa for comparative and evolutionary studies at a molecular level.

Computer-made peptide RQ18 acts as a dual antifungal and antibiofilm peptide though membrane-associated mechanisms of action.

The spread of fungi resistant to conventional drugs has become a threatening problem. In this context, antimicrobial peptides (AMPs) have been considered as one of the main alternatives for controlling fungal infections. Here, we report the antifungal and antibiofilm activity and some clues about peptide RQ18's mechanism of action against Candida and Cryptococcus. This peptide inhibited yeast growth from 2.5 µM and killed all Candida tropicalis cells within 2 h incubation. Moreover, it showed a synergistic effect with antifungal agent the amphotericin b. RQ18 reduced biofilm formation and promoted C. tropicalis mature biofilms eradication. RQ18's mechanism of action involves fungal cell membrane damage, which was confirmed by the results of RQ18 in the presence of free ergosterol in the medium and fluorescence microscopy by Sytox green. No toxic effects were observed in murine macrophage cell lines and Galleria mellonella larvae, suggesting fungal target selectivity. Therefore, peptide RQ18 represents a promising strategy as a dual antifungal and antibiofilm agent that contributes to infection control without damaging mammalian cells.

IL-1ß mediates Candida tropicalis-induced immunosuppressive function of MDSCs to foster colorectal cancer.

BACKGROUND: There is increasing evidence that gut fungi dysbiosis plays a crucial role in the development and progression of colorectal cancer (CRC). It has been reported that gut fungi exacerbate the severity of CRC by regulating tumor immunity. Our previous studies have shown that the opportunistic pathogenic fungal pathogen, Candida tropicalis (C. tropicalis) promotes CRC progression by enhancing the immunosuppressive function of MDSCs and activating the NLRP3 inflammasome of MDSCs. However, the relationship between IL-1ß produced by NLRP3 inflammasome activation and the immunosuppressive function of MDSCs enhanced by C. tropicalis in CRC remains unclear. METHODS: The TCGA database was used to analyze the relationship between IL-1ß and genes related to immunosuppressive function of MDSCs in human CRC. The expression of IL-1ß in human CRC tissues was detected by immunofluorescence staining. The proteomic analysis was performed on the culture supernatant of C. tropicalis-stimulated MDSCs. The experiments of supplementing and blocking IL-1ß as well as inhibiting the NLRP3 inflammasome activation were conducted. A mouse colon cancer xenograft model was established by using MC38 colon cancer cell line. RESULTS: Analysis of CRC clinical samples showed that the high expression of IL-1ß was closely related to the immunosuppressive function of tumor-infiltrated MDSCs. The results of in vitro experiments revealed that IL-1ß was the most secreted cytokine of MDSCs stimulated by C. tropicalis. In vitro supplementation of IL-1ß further enhanced the immunosuppressive function of C. tropicalis-stimulated MDSCs and NLRP3-IL-1ß axis mediated the immunosuppressive function of MDSCs enhanced by C. tropicalis. Finally, blockade of IL-1ß secreted by MDSCs augmented antitumor immunity and mitigated C. tropicalis-associated colon cancer. CONCLUSIONS: C. tropicalis promotes excessive secretion of IL-1ß from MDSCs via the NLRP3 inflammasome. IL-1ß further enhances the immunosuppressive function of MDSCs to inhibit antitumor immunity, thus promoting the progression of CRC. Therefore, targeting IL-1ß secreted by MDSCs may be a potential immunotherapeutic strategy for the treatment of CRC.

Multifarious plant growth-promoting traits of mangrove yeasts: growth enhancement in mangrove seedlings (Rhizophora mucronata) for conservation.

Plant Growth-Promoting Yeasts (PGPY) have garnered significant attention in recent years; however, research on PGPY from mangroves remains a largely unexplored frontier. This study, therefore, focused on exploring the multifaceted plant growth-promoting (PGP) capabilities of yeasts isolated from mangroves of Puthuvype and Kumbalam. The present work found that manglicolous yeasts exhibited diverse hydrolytic properties, with the predominance of lipolytic activity, in addition to other traits such as phosphate solubilization, and production of indole acetic acid, siderophore, ammonia, catalase, nitrate, and hydrogen cyanide. After screening for 15 PGP traits, three strains P 9, PV 23, and KV 35 were selected as the most potent ones. These strains also exhibited antagonistic activity against fungal phytopathogens and demonstrated resilience to abiotic stresses, making them not only promising biocontrol agents but also suited for field application. The potent strains P 9, PV 23, and KV 35 were molecularly identified as Candida tropicalis, Debaryomyces hansenii, and Aureobasidium melanogenum, respectively. The potential of these strains in enhancing the growth performance of mangrove seedlings of Rhizophora mucronata, was demonstrated using the pot-experiment. The results suggested that the consortium of three potent strains (P 9, PV 23, and KV 35) was more effective in increasing the number of shoot branches (89.2%), plant weight (87.5%), root length (83.3%), shoot height (57.9%) and total leaf area (35.1%) than the control seedlings. The findings of this study underscore the significant potential of manglicolous yeasts in contributing to mangrove conservation and restoration efforts, offering a comprehensive understanding of their diverse plant growth-promoting mechanisms and highlighting their valuable role in sustainable ecosystem management.

Carbon substrates promotes stress resistance and drug tolerance in clinical isolates of Candida tropicalis.

Candida tropicalis is a human pathogen and one of the most prevalent non-Candida albicans Candida (NCAC) species causing invasive infections. Azole antifungal resistance in C. tropicalis is also gradually increasing with the increasing incidence of infections. The pathogenic success of C. tropicalis depends on its effective response in the host microenvironment. To become a successful pathogen, cellular metabolism, and physiological status determine the ability of the pathogen to counter diverse stresses inside the host. However, to date, limited knowledge is available on the impact of carbon substrate metabolism on stress adaptation and azole resistance in C. tropicalis. In this study, we determined the impact of glucose, fructose, and sucrose as the sole carbon source on the fluconazole resistance and osmotic (NaCl), oxidative (H2O2) stress adaptation in C. tropicalis clinical isolates. We confirmed that the abundance of carbon substrates influences or increases drug resistance and osmotic and oxidative stress tolerance in C. tropicalis. Additionally, both azole-resistant and susceptible isolates showed similar stress adaptation phenotypes, confirming the equal efficiency of becoming successful pathogens irrespective of drug susceptibility profile. To the best of our knowledge, our study is the first on C. tropicalis to demonstrate the direct relation between carbon substrate metabolism and stress tolerance or drug resistance.

Isolation and characterization of Candida tropicalis B: a promising yeast strain for biodegradation of petroleum oil in marine environments.

The increasing interest in environmental protection laws has compelled companies to regulate the disposal of waste organic materials. Despite efforts to explore alternative energy sources, the world remains heavily dependent on crude petroleum oil and its derivatives. The expansion of the petroleum industry has significant implications for human and environmental well-being. Bioremediation, employing living microorganisms, presents a promising approach to mitigate the harmful effects of organic hydrocarbons derived from petroleum. This study aimed to isolate and purify local yeast strains from oil-contaminated marine water samples capable of aerobically degrading crude petroleum oils and utilizing them as sole carbon and energy sources. One yeast strain (isolate B) identified as Candida tropicalis demonstrated high potential for biodegrading petroleum oil in seawater. Physiological characterization revealed the strain's ability to thrive across a wide pH range (4-11) with optimal growth at pH 4, as well as tolerate salt concentrations ranging from 1 to 12%. The presence of glucose and yeast extract in the growth medium significantly enhanced the strain's biomass formation and biodegradation capacity. Scanning electron microscopy indicated that the yeast cell diameter varied based on the medium composition, further emphasizing the importance of organic nitrogenous sources for initial growth. Furthermore, the yeast strain exhibited remarkable capabilities in degrading various aliphatic and aromatic hydrocarbons, with a notable preference for naphthalene and phenol at 500 and 1000 mg/l, naphthalene removal reached 97.4% and 98.6%, and phenol removal reached 79.48% and 52.79%, respectively. Optimization experiments using multi-factorial sequential designs highlighted the influential role of oil concentration on the bioremediation efficiency of Candida tropicalis strain B. Moreover, immobilized yeast cells on thin wood chips demonstrated enhanced crude oil degradation compared to thick wood chips, likely due to increased surface area for cell attachment. These findings contribute to our understanding of the potential of Candida tropicalis for petroleum oil bioremediation in marine environments, paving the way for sustainable approaches to address oil pollution.

Candida tropicalis-A systematic review to inform the World Health Organization of a fungal priority pathogens list.

In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority fungal pathogens and establish the WHO Fungal Priority Pathogens List for future research. This systematic review aimed to evaluate the features and global impact of invasive candidiasis caused by Candida tropicalis. PubMed and Web of Science were searched for studies reporting on criteria of mortality, morbidity (defined as hospitalization and disability), drug resistance, preventability, yearly incidence, diagnostics, treatability, and distribution/emergence from 2011 to 2021. Thirty studies, encompassing 436 patients from 25 countries were included in the analysis. All-cause mortality due to invasive C. tropicalis infections was 55%-60%. Resistance rates to fluconazole, itraconazole, voriconazole and posaconazole up to 40%-80% were observed but C. tropicalis isolates showed low resistance rates to the echinocandins (0%-1%), amphotericin B (0%), and flucytosine (0%-4%). Leukaemia (odds ratio (OR) = 4.77) and chronic lung disease (OR = 2.62) were identified as risk factors for invasive infections. Incidence rates highlight the geographic variability and provide valuable context for understanding the global burden of C. tropicalis infections. C. tropicalis candidiasis is associated with high mortality rates and high rates of resistance to triazoles. To address this emerging threat, concerted efforts are needed to develop novel antifungal agents and therapeutic approaches tailored to C. tropicalis infections. Global surveillance studies could better inform the annual incidence rates, distribution and trends and allow informed evaluation of the global impact of C. tropicalis infections.

COVID-19 associated candidemia: From a shift in fungal epidemiology to a rise in azole drug resistance.

Our understanding of fungal epidemiology and the burden of antifungal drug resistance in COVID-19-associated candidemia (CAC) patients is limited. Therefore, we conducted a retrospective multicenter study in Iran to explore clinical and microbiological profiles of CAC patients. Yeast isolated from blood, were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and subjected to antifungal susceptibility testing (AFST) using the broth microdilution method M27-A3 protocol. A total of 0.6% of the COVID-19 patients acquired CAC (43/6174). Fluconazole was the most widely used antifungal, and 37% of patients were not treated. Contrary to historic candidemia patients, Candida albicans and C. tropicalis were the most common species. In vitro resistance was high and only noted for azoles; 50%, 20%, and 13.6% of patients were infected with azole-non-susceptible (ANS) C. tropicalis, C. parapsilosis, and C. albicans isolates, respectively. ERG11 mutations conferring azole resistance were detected for C. parapsilosis isolates (Y132F), recovered from an azole-naïve patient. Our study revealed an unprecedented rise in ANS Candida isolates, including the first C. parapsilosis isolate carrying Y132F, among CAC patients in Iran, which potentially threatens the efficacy of fluconazole, the most widely used drug in our centers. Considering the high mortality rate and 37% of untreated CAC cases, our study underscores the importance of infection control strategies and antifungal stewardship to minimize the emergence of ANS Candida isolates during COVID-19.

Systematic metabolic engineering for improved synthesis of perillic acid in Candida tropicalis.

Perillic acid has been studied as an anticancer and antimicrobial drug. Production of perillic acid has attracted considerable attention. Meanwhile, Candida tropicalis is an unconventional diploid yeast, most significantly characterized by its ability to metabolize alkanes or fatty acids for growth and proliferation. Therefore, perillic acid's precursor (L-limonene) in C. tropicalis was firstly synthesized by expressing a Mentha spicata L-limonene synthase gene, LS_Ms in this work. Expression of a gene which encoded for a truncated version of tLS_Ms increased the production of L-limonene with a 2.78-fold increase in the titer over C. tropicalis GJR-LS-01. Compartmentalized expression of the gene tLS_Ms inhibited the production of L-limonene in C. tropicalis compared to cytoplasmic expression. Cytoplasmic overexpression of seven precursor synthesis genes significantly enhanced the production of L-limonene in C. tropicalis compared to their compartmentalized expression (mitochondria or peroxisomes), which increased by 31.7-fold in C. tropicalis GJR-tLS-01. The L-limonene titer in C. tropicalis GJR-EW-tLS-04 overexpressing the mutant gene ERG20WW in the cytoplasm was significantly increased, 11.33-fold higher than the control. The titer of L-limonene for 60 g/L glucose was increased by 1.40-fold compared to the control. Finally, a Salvia miltiorrhiza cytochrome P450 enzyme gene CYP7176 and an Arabidopsis thaliana NADPH cytochrome P450 reductase gene CPR were heterologously expressed in C. tropicalis GJR-EW-tLS-04C for the synthesis of perillic acid, which reached a titer of 106.69 mg/L in a 5-L fermenter. This is the first report of de novo synthesis of perillic acid in engineered microorganisms. The results also showed that other chemicals may be efficiently produced in C. tropicalis. KEY POINTS: • Key genes cytoplasmic expression was conducive to L-limonene production in C. tropicalis. • Perillic acid was first synthesized de novo in engineered microorganisms. • The titer of perillic acid reached 106.69 mg/L in a 5-L fermenter.

One Case of Drug-Resistant Invasive Fungal Infection after Myelodysplastic Syndrome Chemotherapy.

BACKGROUND: The aim of this study was to evaluate the therapeutic regimen of a patient with myelodysplastic syndrome (MDS) who developed invasive fungal infections caused by drug-resistant Candida tropicalis after chemotherapy and to investigate the effect of drug treatment. METHODS: We referred to the Diagnostic Criteria and Treatment Principles of invasive fungal diseases in patients with hematological diseases and malignant tumors (2013, fourth revised edition) and the Expert Consensus on Clinical Application of Posaconazole (2022 Edition). In addition, the drug treatment regimens of drug-resistant Candida tropicalis were reviewed. The doctors in charge were involved in the drug treatment process, and the ra-tional drug use was selected according to evidence-based medicine. RESULTS: After 4 months of use, the nodules around the body disappeared, and there was no further fever during follow-up. After 6 months of use, posaconazole was discontinued, and the patient continued to follow-up for 1 month without further fever or nodules. CONCLUSIONS: The combination of posaconazole, amphotericin B liposome, and micafungin is effective in the treatment of fluconazole-resistant Candida tropicalis infection.

Synergistic activity of gold nanoparticles with amphotericin B on persister cells of Candida tropicalis biofilms.

AIM: The antifungal activity was studied on sessile and persister cells (PCs) of Candida tropicalis biofilms of gold nanoparticles (AuNPs) stabilized with cetyltrimethylammonium bromide (CTAB-AuNPs) and those conjugated with cysteine, in combination with Amphotericin B (AmB). MATERIALS/METHODS: The PC model was used and synergistic activity was tested by the checkerboard assay. Biofilms were studied by crystal violet and scanning electron microscopy. RESULTS/CONCLUSIONS: After the combination of both AuNPs and AmB the biofilm biomass was reduced, with significant differences in architecture being observed with a reduced biofilm matrix. In addition, the CTAB-AuNPs-AmB combination significantly reduced PCs. Understanding how these AuNPs aid in the fight against biofilms and the development of new approaches to eradicate PCs has relevance for chronic infection treatment.

Synergy of histone acetyltransferase inhibitor (HATi) with quercetin inhibits biofilm formation in Candida tropicalis.

Histone acetyltransferase inhibitors (HATi) are mechanism-based inhibitors that show promise in the treatment of several illnesses, including diabetes, hyperlipidemia, cancer, and Alzheimer's disease. The work emphasizes the significance of HATi as a possible treatment strategy against Candida species biofilms. Here, in this study, we found that combining a HATi, anacardic acid (AA), and quercetin, a known flavonoid, significantly prevented biofilm formation by C. tropicalis. We further show that C. tropicalis exhibited a considerable downregulation of drug-resistance gene expression (CDR1 and MDR1) when co-administrated. Additionally, in silico studies revealed that the AA interacts strongly with a histone acetyltransferase, Rtt109, which may account for the observed biofilm inhibitory effect. In conclusion, the study illustrates how HATi may be used to potentiate the inhibitory action of phytoactives or antifungals against drug-resistant yeast infections.

Xylitol biosynthesis enhancement by Candida tropicalis via medium, process parameter optimization, and co-substrate supplementation.

The present study examines the impact of nitrogen sources (yeast extract, ammonium sulfate peptone, ammonium nitrate, urea, and sodium nitrate), salt solution (0.5 g/L MgSO4, 0.5 g/L KH2PO4, 0.3 g/L CaCl2), trace elements solution (0.1 g/L CuSO4, 0.1 g/L FeSO4, 0.02 g/L MnCl2, 0.02 g/L ZnSO4), operational parameters (temperature, aeration, agitation, initial pH and xylose concentration) and co- substrate supplementation (glucose, fructose, maltose, sucrose, and glycerol) on xylitol biosynthesis by Candida tropicalis ATCC 13803 using synthetic xylose. The significant medium components were identified using the Plackett Burman design followed by central composite designs to obtain the optimal concentration for the critical medium components in shaker flasks. Subsequently, the effect of operational parameters was examined using the One Factor At a Time method, followed by the impact of five co-substrates on xylitol biosynthesis in a 1 L bioreactor. The optimal media components and process parameters are as follows: peptone: 12.68 g/L, yeast extract: 6.62 g/L, salt solution (0.5 g/L MgSO4, 0.5 g/L KH2PO4, and 0.3 g/L CaCl2): 1.23 X (0.62 g/L, 0.62 g/L, and 0.37 g/L respectively), temperature: 30 °C, pH: 6, agitation: 400 rpm, aeration: 1 vvm, and xylose: 50 g/L. Optimization studies resulted in xylitol yield and productivity of 0.71 ± 0.004 g/g and 1.48 ± 0.018 g/L/h, respectively. Glycerol supplementation (2 g/L) further improved xylitol yield (0.83 ± 0.009 g/g) and productivity (1.87 ± 0.020 g/L/h) by 1.66 and 3.12 folds, respectively, higher than the unoptimized conditions thus exhibiting the potential of C. tropicalis ATCC 13803 being used for commercial xylitol production.

Detoxification of areca nut acid hydrolysate and production of xylitol by Candida tropicalis (MTCC 6192).

Areca nut husk is the most promising alternative source of low-cost raw materials because it contains a considerable amount of five-carbon monosaccharide sugar in the form of xylose. This polymeric sugar can be isolated and transformed into a value-added chemical using fermentation. To extract sugars from areca nut husk fibers, preliminary pretreatment, such as dilute acid hydrolysis (H2SO4), was performed. The hemicellulosic hydrolysate of areca nut husk can produce xylitol through fermentation, but toxic components inhibit the growth of microorganisms. To overcome this, a series of detoxification treatments, including pH adjustment, activated charcoal, and ion exchange resin, were carried out to reduce the concentration of inhibitors in the hydrolysate. This study reports a remarkable 99% removal of inhibitors in the hemicellulosic hydrolysate. Subsequently, a fermentation process using Candida tropicalis (MTCC6192) was executed with the detoxified hemicellulosic hydrolysate of areca nut husk, yielding an optimum xylitol yield of 0.66 g/g. This study concludes that detoxification techniques like pH adjustment, activated charcoal, and ion exchange resins are the most economical and effective methods for eliminating toxic compounds in hemicellulosic hydrolysates. Therefore, the medium derived after detoxification from areca nut hydrolysate may be considered to have significant potential for xylitol production.

Synergistic Antifungal Effect and In Vivo Toxicity of a Monoterpene Isoespintanol Obtained from Oxandra xylopioides Diels.

Candida sp. infections are a threat to global health, with high morbidity and mortality rates due to drug resistance, especially in immunocompromised people. For this reason, the search for new alternatives is urgent, and in recent years, a combined therapy with natural compounds has been proposed. Considering the biological potential of isoespintanol (ISO) and continuing its study, the objective of this research was to assess the effect of ISO in combination with the antifungals fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP) against clinical isolates of C. tropicalis and to evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84) in female mice (Mus musculus) of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. An evaluation of the mice via direct observation showed no behavioral changes or variations in weight during treatment; furthermore, an analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process. In addition, histopathological studies of the lungs, liver and kidneys showed no signs of toxicity caused by ISO. This was consistent with an analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated, placing it as a monoterpene of interest in the search for compounds with pharmacological potential.

Investigation of adhesion status of Candida species to the surface of resin materials produced at different angles with additive manufacturing.

BACKGROUND: The aim of this study was to evaluate the adhesion of Candida glabrata, Candida albicans, Candida krusei, Candida parapsilosis and Candida tropicalis yeasts to disk-shaped resin materials produced from resin which used in the production of surgical guide with 0, 45 and 90-degrees printing orientations by Liquid Crystal Display additive manufacturing technology. METHODS: Disk-shaped specimens were printed with surgical guide resin using the Liquid Crystal Display production technique in 3 printing orientations (0, 45 and 90-degrees). Surface roughness and contact angle values were evaluated. Real-Time PCR analysis was performed to evaluate Candida adhesion (C. glabrata, C. albicans, C. krusei, C. parapsilosis and C. tropicalis) Field emission scanning electron microscope (FESEM) images of the materials were obtained. RESULTS: Specimens oriented at 45-degrees demonstrated higher surface roughness (P < .05) and lower contact angle values than other groups. No significant difference was found in the adhesion of C. glabrata, C. albicans, and C. parapsilosis among specimens printed at 0, 45, and 90-degrees orientations (P > .05). A higher proportion of C. krusei and C. tropicalis was found in the specimens printed at orientation degrees of 45 = 90 < 0 with statistical significance. Analyzing the adhesion of all Candida species reveals no statistical disparity among the printing orientations. CONCLUSIONS: The surface roughness, contact angle, and adhesion of certain Candida species are affected by printing orientations. Hence, careful consideration of the printing orientation is crucial for fabricating products with desirable properties. In 45-degree production, roughness increases due to the layered production forming steps, whereas in 0-degree production, certain Candida species exhibit high adhesion due to the formation of porous structures. Consequently, considering these factors, it is advisable to opt for production at 90-degrees, while also considering other anticipated characteristics.

Candida Tropicalis Endocarditis: A case report and literature review.

Fungi rarely cause infective endocarditis but when they do, they are often associated with poor outcomes. Candida tropicalis accounts for only 10% of Candida endocarditis cases. A case of a 30-year-old male with a history of intravenous drug abuse was reported to the emergency department in August, 2021 with right-sided leg pain and fever for 3 days. A trans-thoracic echocardiogram showed a vegetation on the aortic valve and a computed tomography angiogram showed complete nonopacification of the right-sided common iliac artery and the superficial femoral artery just distal to its branching of the right profunda femoris artery. An emergent right iliofemoral embolectomy was done. Candida tropicalis was isolated from tissue and blood cultures. The patient was successfully treated with aortic valve replacement and intravenous caspofungin. The other reported cases of Candida tropicalis were reviewed and findings were compared with those reported in patients with Candida albicans and Candida parapsilosis endocarditis.

Candida tropicalis oligopeptide transporters assist in the transmembrane transport of the antimicrobial peptide CGA-N9.

Candida tropicalis is often reported as the second or third most common pathogen causing fungal infections. Antimicrobial peptides (AMPs) have attracted increasing attention for their broad-spectrum antimicrobial properties and low cytotoxicity. Our previous studies have shown that CGA-N9, a non-membrane-rupturing AMP, crosses the cell membrane to exert anticandidal activity. We speculate that there are some related transporters that assist in the transmembrane transport of CGA-N9. In this study, the relationship between CGA-N9 lethality kinetics and its real-time transmembrane amount in C. tropicalis cells was investigated. The results demonstrated that there was a positive correlation between its candicidal activity and transmembrane amount. A total of 12 oligopeptide transporter (OPT) coding sequences (CDSs) were cloned from C. tropicalis by using the conservative OPT gene sequences of Candida spp. to design primers and were named C. tropicalis OPTs (CtOPTs). The results of RT‒qPCR demonstrated that the expression levels of CtOPT1, CtOPT9 and CtOPT12 were correlated with the CGA-N9 transmembrane amount in a time-dependent manner. The results of molecular docking demonstrated that CtOPT1, CtOPT9 and CtOPT12 interact strongly with CGA-N9. Therefore, CtOPT1, CtOPT9 and CtOPT12 were predicted to assist in the transmembrane transport of the AMP CGA-N9.