Fungal Infections Research Articles

Redevelopment of natural eugenol as potential pesticidal resource: New insights into synthesis and antifungal evaluation of eugenol-derived Schiff bases with reactive oxygen species behavior

Natural products have ancient history as fascinating sources of pharmaceuticals, agrochemicals as well as NPs-derived drug/pesticide innovation. Its diversiform biological performance and skeleton diversity enable to fill the drug/pesticide discovery pipeline in response to the growing innovation demand. Eugenol, a naturally occurring phenolic compound from plant Eugenia caryophyllata, have been attracting attention in agricultural application. To further extend its value-added utilizations in agricultural application and elucidate the underlying molecule mechanism, the 35 of novel eugenol-derived Schiff bases were herein skillfully prepared by means of natural-products modification strategy. Interestingly, the antifungal activity results indicated that the optimal antifungal molecule was A10, affording an EC50 of 0.850 μg/mL toward Botryosphaeria dothidea (B. d.), which was superior to those of parent eugenol (EC50 > 100 μg/mL) and ferimzone (EC50 > 100 μg/mL). It was illustrated that introduction of Schiff base scaffold into natural eugenol contributed to enhance the antifungal performance. Furthermore, a series of bioassays showed the antifungal behavior of compound A10, which had a powerful disruptive effect on the membrane by triggering reactive oxygen species production in the mycelium. Taken together, this study redeveloped natural eugenol as potential antifungal candidates to control fungal infections by triggering reactive oxygen species production.

Evaluation of Crushed Posaconazole Delayed Release Tablets in Lung Transplant Recipients.

Invasive fungal infections can cause serious complications after lung transplant; therefore, prophylaxis with posaconazole is common. The posaconazole delayed-release (DR) tablet is preferred. Although the package insert states DR tablets cannot be crushed, recent data suggest it is reasonable. We hypothesized that crushed posaconazole DR tablets could reach therapeutic levels in lung transplant recipients. A retrospective study of lung transplant recipients between January 2018 and July 2023, who received crushed posaconazole DR for at least 5 days was completed. Posaconazole troughs were evaluated, and differences were compared between subjects who were therapeutic to those who were subtherapeutic. A cost analysis was also performed. Thirty subjects received crushed posaconazole DR and 50% were therapeutic. The median trough was 1mg/L for those who were therapeutic and 0.4mg/L for those who were not (p < 0.001). The median cumulative dose was 2000mg, and there were no significant differences in the incidence of diarrhea or tube feeds. More subjects in the therapeutic group were loaded (33%vs. 13%), although this was not statistically significant (p = 0.39). No subjects had breakthrough aspergillus one month after starting crushed therapy. Crushed posaconazole DR tablets are a viable and cost savings option, but loading doses and higher maintenance doses may be required to reach therapeutic levels. Those who received loading doses (intravenously or crushed) followed by a daily crushed dose of 400mg were more likely to be therapeutic. Limitations of our study include that it is single-center, small in sample size, and retrospective.

OsPIPK-FAB, A Negative Regulator in Rice Immunity Unveiled by OsMBL1 Inhibition

Phosphatidylinositol signaling system plays a crucial role in plant physiology and development, phosphatidylinositol phosphate kinases (PIPKs) are one of the essential enzymes responsible for catalyzing the synthesis of phosphatidylinositol bisphosphate (PIP2) within this signaling pathway. However, its mechanism of signal transduction remains poorly exploited in plants. OsMBL1, a jacalin-related mannose-binding lectin in rice, plays a crucial role in plant defense mechanisms, acting as a key component of the pattern-triggered immunity (PTI) pathway. Here, a rice phosphatidylinositol-phosphate kinase FAB (OsPIPK-FAB), a member of the rice PIPKs family, as an interacting protein of OsMBL1 through yeast-two-hybrid (Y2H) screening assay. And this interaction was confirmed by using co-immunoprecipitation (Co-IP) and pull-down assay techniques. Furthermore, we demonstrated that the deletion of OsPIPK-FAB gene in plant enhanced resistance against rice blast while overexpression of OsPIPK-FAB increases sensitivity to the fungal infection. Additionally, through determination and measurement of the plant inositol 1,4,5-trisphosphate (IP3) contents and the plant phosphatidylinositol 4-phosphate 5-kinase (PIP5K) activity, we revealed that OsMBL1 inhibits the PIP5K kinase activity of OsPIPK-FAB as well as the plant IP3 contents in rice. Conclusively, these findings indicated that OsPIPK-FAB serves as a novel and critical component that is negatively involved in PTI activation and was inhibited by OsMBL1.

Copper acquisition is essential for plant colonization and virulence in a root-infecting vascular wilt fungus.

Plant pathogenic fungi provoke devastating agricultural losses and are difficult to control. How these organisms acquire micronutrients during growth in the host environment remains poorly understood. Here we show that efficient regulation of copper acquisition mechanisms is crucial for plant colonization and virulence in the soilborne ascomycete Fusarium oxysporum, the causal agent of vascular wilt disease in more than 150 different crops. Using a combination of RNA-seq and ChIP-seq, we establish a direct role of the transcriptional regulator Mac1 in activation of copper deficiency response genes, many of which are induced during plant infection. Loss of Mac1 impaired growth of F. oxysporum under low copper conditions and abolishes pathogenicity on tomato plants and on the invertebrate animal host Galleria mellonella. Importantly, overexpression of two Mac1 target genes encoding a copper reductase and a copper transporter was sufficient to restore virulence in the mac1 mutant background. Our results establish a previously unrecognized role of copper reduction and uptake in fungal infection of plants and reveal new ways to protect crops from phytopathogens.

Ancient duplications, multidimensional specializations, and defense role of hexokinases in wheat.

Hexokinases (HXKs), which sense and catalyze cellular sugar, play a critical role in the growth and development of various plants, including wheat, a primary source of human calories frequently attacked by fungal pathogens. However, the evolutionary dynamics and functional diversification of HXKs in wheat, particularly their roles in plant defense, remain unclear. Here, we discovered that the wheat hexokinase gene family originated through multiple ancient gene duplications across different plant lineages and has undergone comprehensive, multidimensional functional specialization in gene expression, subcellular localization, enzyme activity, and regulation of plant defense responses. Gene expression analysis suggests that two-thirds of the TaHXK genes are responsive to fungal infection. Subcellular analysis reveals that while six TaHXKs are localized in mitochondria, three TaHXKs from different phylogenetic branches are sorted into other cellular compartments. Notably, biochemical analysis shows that TaHXKs in mitochondria differ in their glucose-catalyzing activity, with TaHXK5 and TaHXK3 exhibiting the highest and lowest enzyme activity, respectively. Consistently, transient expression analysis suggests that TaHXK5 induces various plant defense responses, while TaHXK3 is defective in activating some plant defense responses. Furthermore, inactivation of the glucokinase activity of TaHXK5 compromised its function in defense activation, suggesting that mitochondrial TaHXKs display functional divergence in both enzyme activity and defense-inducing activity that are intrinsically connected. Overall, our findings reveal that the multidimensional specialization events following the ancient duplication events may have shaped the functional diversity of HXKs in wheat, shedding light on their evolutionary dynamics and potentially contributing to the improvement of wheat defense.

Predicting fungal infection sensitivity of sepals in harvested tomatoes using imaging spectroscopy and partial least squares discriminant analysis

Tomatoes ( Solanum lycopersicum L.) are a widely grown and globally traded vegetable, essential for both local consumption and international trade. However, approximately 30% of harvested tomato yields are lost due to fungal decay during postharvest handling. Timely disease identification is crucial to prevent such losses, but certain tomato varieties exhibit higher susceptibility to fungal infections than others. Additionally, there are variations in susceptibility among individual sepals, with unknown underlying causes. Traditional methods for assessing fungal presence in plants have limitations, such as sample destruction and a focus on symptom detection rather than evaluating susceptibility to fungal infection. Hence, there is a demand need for an accurate, non-destructive method capable of predicting susceptibility to fungal infection. The use of hyperspectral imaging (HSI) with chemometrics presents a pioneering approach to address this need. In this study, three tomato cultivars (‘Brioso,’ ‘Cappricia,’ and ‘Provine’) were studied. Hyperspectral images were captured on day-1 of harvest, followed by controlled fungal growth conditions. Ground truth assessments were conducted by three experts on day-3 and day-4, averaging severity scores assigned per sepal. The methodology involved extracting spectra from HSI images and calibrating and validating models using partial least squares discriminant analysis (PLSDA), aiming to optimize model parameters for accurate predictions. The models were categorized into those developed using data from a single variety (intravariety) and those utilizing data from multiple varieties combined (global models). The best-performing intravariety model was established using the Cappricia variety, achieving a balanced accuracy of 0.84. Conversely, a global model combining Cappricia and Provine varieties achieved a balanced accuracy of 0.70. Overall, the results suggest that distinguishing between more and less susceptible sepals is feasible under controlled conditions.

Genome-Wide Analysis of the Serine Carboxypeptidase-like (SCPL) Protein Family of Bitter Gourd and Functional Validation of McSCPL22 in Fusarium oxysporum f. sp. Momordicae (FOM) Resistance.

Bitter gourd is increasingly being recognized for its value as a vegetable and medicinal use, but the molecular mechanisms of pathogen resistance remain relatively poorly understood. The serine carboxypeptidase-like (SCPL) protein family plays a key role in plant growth, pathogen defense, and so on. However, a comprehensive identification and functional characterization of the SCPL gene family has yet to be conducted in bitter melon. In this study, 32 SCPL genes were identified in bitter gourd and divided into three classes. The number of SCPL genes contained in the three clusters was 7, 7, and 18, respectively. Most SCPL gene promoters contain cis-acting elements with light, hormone, and stress responses. The RNA sequencing data showed that the expression of several SCPL genes changed significantly after pathogen infection. In particular, expression of the McSCPL4, 10, 17, 22, and 25 genes increased substantially in the resistant varieties after infection, and their expression levels were higher than those in the susceptible varieties. These results suggested that genes such as McSCPL4, 10, 17, 22, and 25 may play a significant role in conferring resistance to fungal infections. Moreover, the expression levels of the McSCPL10, 17, 22, 23, and 25 genes were likewise significantly changed after being induced by salicylic acid (SA) and jasmonic acid (JA). In situ hybridization showed that McSCPL22 was expressed in the vascular tissues of infected plants, which largely overlapped with the location of Fusarium oxysporum f. sp. Momordicae (FOM) infection and the site of hydrogen peroxide production. Our results showed that McSCPL22 may be involved in the regulation of the SA and JA pathways and enhance resistance to FOM in bitter gourd plants. This is the first study to perform SCPL gene family analysis in bitter gourd. McSCPL22 may have the potential to enhance FOM resistance in bitter gourd, and further investigation into its function is warranted. The results of this study may enhance the yield and molecular breeding of bitter gourd.

A Case of Massive Haemoptysis due to Aneurysm of Left Pulmonary Artery in Patient of COVID 19 with Invasive Fungal Infection

A Case of Massive Haemoptysis due to Aneurysm of Left Pulmonary Artery in Patient of COVID 19 with Invasive Fungal Infection

Timeline and outcomes of viral and fungal infections after Chimeric Antigen Receptor (CAR) T-cell therapy: A large database analysis

ObjectivesThis large database analysis aims to describe the incidence, timeline, and risk factors for viral and fungal infections after chimeric antigen receptor (CAR) T-cell therapy. MethodsWe queried a global research network database, TriNetX, for patients who received CAR T-cell therapy, who were identified and followed for the development of viral and fungal infections. Baseline demographic, oncologic history, laboratory data and medication histories were collected. We evaluated risk factors for respiratory viral infections (RVI), herpesvirus, fungal infections and mortality using Cox regression. ResultsA total of 2,256 patients who received CAR T-cell therapy were included, 1,867 (82.7%) were CD19-targeted and 400 (17.7%) were BCMA-targeted. Following CAR T-cell infusion, RVI were the most prevalent (23.3%) with a median onset of 160 days (IQR 52-348 days), while herpesvirus and fungal infections were less frequent, occurring in 13.6% and 11.4% of cases with median onsets of 71 (IQR 18-252) and 73 days (IQR 14-236 days), respectively. On multivariable Cox regression, independent predictors of RVI included acute lymphoblastic leukemia (ALL, HR 1.61), prior hematopoietic cell transplant (HCT, HR 1.29), cytokine release syndrome (CRS, HR 1.41), hemophagocytic lymphohistiocytosis (HLH, HR 1.96), and glucocorticoids (HR 3.37). Prior HCT (HR 2.00), hypogammaglobulinemia (HR 1.51), immune-effector cell-associated neurotoxicity syndrome (ICANS, HR 1.52), and HLH (HR 1.99) were associated with a higher risk of herpesviruses. Independent predictors of fungal infections included prior HCT (HR 1.59), CRS (HR 1.58) and hypogammaglobulinemia (HR 1.40). Idecabtagene vicleucel was associated with a lower risk of herpesvirus and fungal infections (HR 0.39 and 0.44, respectively). ConclusionsIn a large cohort of CAR T-cell therapy recipients, respiratory viral infections were the most common but occurred later, while herpesvirus and fungal infections were less frequent but occurred earlier. Prospective studies investigating prophylaxis and pre-emptive monitoring strategies are needed in this population.

Nanoformulations Insights: A Novel Paradigm for Antifungal Therapies and Future Perspectives.

Currently, fungal infections are becoming more prevalent worldwide. Subsequently, many antifungal agents are available to cure diseases like pemphigus, athlete's foot, acne, psoriasis, hyperpigmentation, albinism, and skin cancer. Still, they fall short due to pitfalls in physiochemical properties. Conventional medications like lotion, creams, ointments, poultices, and gels are available for antifungal therapy but present many shortcomings. They are associated with drug retention and poor penetration problems, resulting in drug resistance, hypersensitivity, and diminished efficacy. On the contrary, nanoformulations have gained tremendous potential in overcoming the drawbacks of conventional delivery. Furthermore, the potential breakthroughs of nanoformulations are site-specific targeting. It has improved bioavailability, patient-tailored approach, reduced drug retention and hypersensitivity, and improved skin penetration. Nowadays, nanoformulations are gaining popularity for antifungal therapy against superficial skin infections. Nanoformulations-based liposomes, niosomes, nanosponges, solid lipid nanoparticles, and potential applications have been explored for antifungal therapy due to enhanced activity and reduced toxicity. Researchers are now more focused on developing patient-oriented target-based nano delivery to cover the lacunas of conventional treatment with higher immune stimulatory effects. Future direction involves the construction of novel nanotherapeutic devices, nanorobotics, and robust methods. In addition, for the preparations of nanoformulations for clinical studies, animal modeling solves the problems of antifungal therapy. This review describes insights into various superficial fungal skin infections and their potential applications, nanocarrier-based drug delivery, and mechanism of action. In addition, it focuses on regulatory considerations, pharmacokinetic and pharmacodynamic studies, clinical trials, patents, challenges, and future inputs for researchers to improve antifungal therapy.

Construction and evaluation of transdermal delivery system of terbinafine-loaded plant exosomes for the treatment of cutaneous fungal infections

Local transdermal of antifungal agents is a problem that limits the effectiveness of clinical treatment of dermatomycosis. In this study, cucumber-derived plant extracellular vesicles (PEV) were extracted and loaded with the antifungal drug terbinafine (TBF) to form TBF-PEV, which was applied locally to the site of skin fungal infection to improve the transdermal transport capacity of TBF and the antifungal effect in vitro and in vivo. Chemical enhancer and physical enhancer methods were replaced by low immunogenicity and non-irritating PEV. TBF-PEV caused obvious curling and wrinkling in the skin, induced changes in the distribution of skin lipids, and changed the structure and content of skin lipids and proteins, thereby increasing the transdermal efficiency of TBF. The local drug concentration was increased, and the antifungal effect was improved in vitro and in vivo. It was first found that PEV inhibited the growth of Candida albicans with high efflux pump expression. In general, this paper has certain significance in local transdermal treatment of fungal skin infections and reversal of fungal resistance.

Risk Factors for Cytomegalovirus Infection after Haematopoietic Stem Cell Transplantation: A Meta-Analysis.

Cytomegalovirus (CMV) infection is the most common viral infection after haematopoietic stem cell transplantation (HSCT). However, studies on related risk factors give different views without any clear conclusion. Therefore, the purpose of this study was to evaluate the risk variables of CMV infection after HSCT in order to provide recommendations for therapeutic treatment. The National Knowledge Infrastructure [CNKI], Chinese Biomedical Literature database [SinoMed], Wanfang Digital Periodicals [WANFANG] and China Science and Technology Journal [VIP] databases, as well as PubMed, Embase, CENTRAL, Web of Science databases were searched. The search keyword was Cumulative Index of Nursing and Related Health Literature (CINAHL). The search time spanned from the time when the database was created to February 2023. Based on inclusion and exclusion criteria, two researchers independently chose the literature, retrieved data, and assessed the bias risk. The methodological quality of the included studies was assessed by the Newcastle Ottawa scale (NOS). A total of 1,038 literatures were retrieved, of which, 18 studies were finally included. The final results of meta-analysis showed that there were seven risk factors as follows: Acute graft-versus-host disease (aGVHD) grades II-IV (II-IV) [odds ratio = 3.39, 95% CI (2.13, 5.41), p <0.05]; ant-thymocyte globulin (ATG) administration in treatment [odds ratio = 2.53, 95% CI (1.41, 4.53), p <0.05]; cyclosporine level after transplantation (>300 ng/ml) [OR = 3.79, 95% CI (1.24, 11.65), p <0.05]; age [odds ratio = 1.83, 95% CI (1.06, 3.15), p <0.05]; neutrophil deficiency time [odds ratio = 6.58, 95% CI (2.24, 19.30), p <0.05]; CMV infection in recipients before transplantation [odds ratio = 6.32,95% CI (4.03, 9.90), p <0.05]; fungal infection [odds ratio = 2.63, 95% CI (1.09, 6.34), p <0.05]. This study preliminarily revealed that CMV infection after HSCT is related to aGVHD (II-IV), ATG administration in pretreatment, cyclosporine level (>300 ng/ml) after transplantation, age, neutrophil deficiency time, CMV infection in recipients before transplantation and fungal infection. However, the mechanisms behind the risk variables are unclear. Further research is necessary to understand the risk factors and to enhance the care of patients with these risk factors to prevent or control infection. Key Words: Haematopoietic stem cell transplantation, Cytomegalovirus infection, Risk factors, Meta-analysis.

Risk Factors for Multidrug Resistance in Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Nomogram.

Our aim was to determine the risk factors for multidrug resistance in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP). The information of 196 patients with Klebsiella pneumoniae infection was collected. The patients were subsequently assigned to the carbapenem-resistant, multidrug-resistant, and non-multidrug-resistant groups. The risk factors for multidrug resistance in CRKP patients were assessed via least absolute shrinkage and selection operator and logistic regression analyses. Moreover, a nomogram was constructed dependent on the identified risk factors, and calibration and decision curves were plotted to detect its accuracy. Length of stay (LOS) [odds ratio (OR) and 95% confidence interval (CI): 4.558 (1.157-17.961), P = 0.030], intensive care unit (ICU) stay within 30 days [OR and 95% CI: 12.643 (3.780-42.293), P < 0.001], Glasgow Coma Scale (GCS) score [OR and 95% CI: 13.569 (2.738-67.236), P = 0.001], fungal infection [OR and 95% CI: 6.398 (1.969-20.785), P = 0.002], and cardiovascular disease (CVD) [OR and 95% CI: 3.871 (1.293-11.592), P = 0.016] were identified as risk factors for multidrug resistance in CRKP patients. The concordance index (C-index) of the constructed nomogram was 0.950 (95% CI: 0.945-0.955). Moreover, decision curve analysis elucidated the nomogram utilization across a wide range of probability thresholds, ranging from 1% to 100%. Finally, internal validation using random data validated the robustness of the predictive model, yielding a C-index of 0.937. The LOS, ICU stay within 30 days, GCS score, fungal infection, and CVD were recognized as risk factors for multidrug resistance in CRKP patients. The constructed nomogram could accurately predict multidrug-resistant CRKP infections in patients.

Risk Factors for Cytomegalovirus Infection after Haematopoietic Stem Cell Transplantation: A Meta-Analysis.

Cytomegalovirus (CMV) infection is the most common viral infection after haematopoietic stem cell transplantation (HSCT). However, studies on related risk factors give different views without any clear conclusion. Therefore, the purpose of this study was to evaluate the risk variables of CMV infection after HSCT in order to provide recommendations for therapeutic treatment. The National Knowledge Infrastructure [CNKI], Chinese Biomedical Literature database [SinoMed], Wanfang Digital Periodicals [WANFANG] and China Science and Technology Journal [VIP] databases, as well as PubMed, Embase, CENTRAL, Web of Science databases were searched. The search keyword was Cumulative Index of Nursing and Related Health Literature (CINAHL). The search time spanned from the time when the database was created to February 2023. Based on inclusion and exclusion criteria, two researchers independently chose the literature, retrieved data, and assessed the bias risk. The methodological quality of the included studies was assessed by the Newcastle Ottawa scale (NOS). A total of 1,038 literatures were retrieved, of which, 18 studies were finally included. The final results of meta-analysis showed that there were seven risk factors as follows: Acute graft-versus-host disease (aGVHD) grades II-IV (II-IV) [odds ratio = 3.39, 95% CI (2.13, 5.41), p <0.05]; ant-thymocyte globulin (ATG) administration in treatment [odds ratio = 2.53, 95% CI (1.41, 4.53), p <0.05]; cyclosporine level after transplantation (>300 ng/ml) [OR = 3.79, 95% CI (1.24, 11.65), p <0.05]; age [odds ratio = 1.83, 95% CI (1.06, 3.15), p <0.05]; neutrophil deficiency time [odds ratio = 6.58, 95% CI (2.24, 19.30), p <0.05]; CMV infection in recipients before transplantation [odds ratio = 6.32,95% CI (4.03, 9.90), p <0.05]; fungal infection [odds ratio = 2.63, 95% CI (1.09, 6.34), p <0.05]. This study preliminarily revealed that CMV infection after HSCT is related to aGVHD (II-IV), ATG administration in pretreatment, cyclosporine level (>300 ng/ml) after transplantation, age, neutrophil deficiency time, CMV infection in recipients before transplantation and fungal infection. However, the mechanisms behind the risk variables are unclear. Further research is necessary to understand the risk factors and to enhance the care of patients with these risk factors to prevent or control infection. Key Words: Haematopoietic stem cell transplantation, Cytomegalovirus infection, Risk factors, Meta-analysis.

Response to Cohen, “Tattoo complications: Neutrophilic dermatoses, viral and systemic fungal infections, and neoplasms"

Response to Cohen, “Tattoo complications: Neutrophilic dermatoses, viral and systemic fungal infections, and neoplasms"

A deep learning approach to detect diseases in pomegranate fruits via hybrid optimal attention capsule network

In 2022, the production rate of pomegranate is estimated at approximately 4.8 million metric tons. Unfortunately, these fruits are susceptible to many different kinds of diseases caused by bacterial, viral, and fungal infections. Such diseases can have a major negative impact on fruit quality, production, and the profitability of pomegranate cultivation. Nowadays, several machine learning and deep learning methods are used to identify pomegranate fruit diseases automatically and effectively. In post-harvest pomegranate fruit disease detection, deep learning has great potential to extract complex patterns and features from large datasets. This can improve disease identification accuracy, enabling more efficient disease control, lower crop losses, and better resource management. The proposed work introduces an intelligent deep learning-based approach for accurately detecting pomegranate diseases, begins with Improved Guided Image Filtering (Improved GIF) and resizing to pre-process fruit images, followed by feature extraction (shape, color, texture) using GLCM and GLRLM to streamline classification. Extracted features are then fed into a novel Hybrid Optimal Attention Capsule Network (Hybrid OACapsNet), which classifies the images as normal or diseased, conditions such as bacterial blight, heart rot, and scab. Our analysis indicates that the proposed classifier has a classification accuracy of 99.19 %, precision of 98.45 %, recall of 98.41 %, F1-score of 98.43 %, and specificity of 99.45 % compared to other techniques. So this approach offers a, which is a feasible solution for automated detection of diseases in fruits, thereby benefiting farmers and supporting their farming operations.

Antifungal peptide-loaded alginate microfiber wound dressing evaluated against Candida albicans in vitro and ex vivo

Invasive fungal infections have high mortality rates, and many current antimycotics are limited by host toxicity and drug resistance. Recent experiments in our laboratory have demonstrated the antifungal activity of dKn2-7, a synthetic peptide, against Candida albicans. The purpose of the current study was to develop a wound dressing capable of dKn2-7 release for extended periods to help combat fungal infection in wounds. dKn2-7 was incorporated into calcium alginate microfibers, an excipient with known wound healing and hemostatic properties. dKn2-7 release rates from the fibers were dependent on drug loading, but all formulations exhibited a burst release with 41–71 % of total release in the first 15 min and 84–96 % release by 24 h. Calcium release at 15 min was similar to that of a commercial hemostatic dressing, indicating dKn2-7 loading would not adversely affect the hemostatic capability of the alginate fibers. In vitro antifungal studies indicated a dose dependent effect with fibers loaded at ≥20 µg/mg causing significant planktonic killing and ≥30 µg/mg causing significant biofilm killing. Viable fungal counts in biofilms grown on ex vivo porcine skin declined by 99 % following 500 µg/mg fiber treatment. Skin histology indicated no significant differences in tissue damage between treatment groups and controls. Results confirm calcium alginate microfibers are capable of binding and subsequently releasing dKn2-7 over a 24-h period when rehydrated. Furthermore, dKn2-7 released from the fibers was able to significantly reduce biofilms in an ex vivo model with minimal toxicity, indicating these dKn2-7 loaded fiber dressings may be effective at controlling C. albicans biofilm infections in vivo.

Optimizing treatment outcomes in acute-on-chronic liver failure: the role of T2candida panel in detecting invasive candidiasis

IntroductionAcute-on-Chronic Liver Failure(ACLF) is a syndrome characterized by organ dysfunction and high mortality in cirrhotic patients. ACLF has multiple triggers but those precipitated by fungal infection have higher mortality. Early detection and treatment of candidemia have shown mortality benefits in ACLF. The sensitivity of blood cultures ranged from 21% - 71%. Given the increase in mortality, it is vital to have a quick yet reliable diagnostic test for the detection of candida. This study examines the risk of developing ACLF and its impact on survival in hospitalized cirrhotic patients with invasive fungal infection via a positive T2Candida Panel. We also examine the effects of earlier treatment on mortality in those with a positive T2Candida Panel. MethodsWe performed a retrospective study and included cirrhotic patients admitted from 2017-2021. Data collected includes baseline characteristics, labs, progression to ACLF, and mortality outcomes. The stages of ACLF were determined through the use of the CLIF-Consortium ACLF score. ResultsOf the 489 patients sampled, 95 patients developed ACLF during the time of the T2 panel collection, of which 60 (63.2%) (p≤0.001) patients had a positive T2Candida Panel. The data also demonstrates that patients who had earlier antifungal initiation had a decrease in mortality (6.15 ± 5.23 versus 13.53 ± 11.42)(p≤001). ConclusionOur study shows that a positive T2 Panel leads to more frequent progression of ACLF and worsening survival outcomes. This study shows that earlier treatment of candidiasis via the T2 Panel leads to mortality benefits.

Perspectives on blastomycosis in Canada in the face of climate change.

Blastomycosis is a disease of potentially varied presentations caused by thermally dimorphic fungi that appear as mold at ambient temperatures and transform to yeast at body temperature. Inhalation of aerosolized fungal spores represents the primary mode of transmission. Exposure may follow outdoor activities that disturb soil, which is warm, moist, acidic and rich in organic debris, particularly within forested areas and in proximity to waterways. Blastomycosis is endemic to several parts of Canada, but is only reportable in Ontario and Manitoba, with Northwestern Ontario being considered a hyperendemic area with average annual incidence rates of over 25 cases per 100,000 population. Delays in diagnosis and treatment are frequently observed as the symptoms and imaging findings of blastomycosis may initially be mistaken for community-acquired pneumonia, tuberculosis or malignancy, which can result in interim disease progression and worsening clinical outcomes. Risks from fungal infections such as blastomycosis are likely to increase with climate change-associated shifts in temperature and rainfall, and this may contribute to the geographic expansion of cases, a phenomenon that appears to be already underway. Further research investigating the ecological niche of Blastomyces and its climate sensitivity could help facilitate better modelling of the potential impacts of climate change on risks to Canadians and inform more effective methods of exposure prevention. Early clinical recognition and treatment of blastomycosis remain the key to minimizing morbidity and mortality.

An Insight into the Repurposing of Phytoconstituents obtained from Delhi's Aravalli Biodiversity Park as Antifungal Agents.

The global prevalence of fungal infections is alarming in both the pre- and post- COVID period. Due to a limited number of antifungal drugs, there are hurdles in treatment strategies for fungal infections due to toxic potential, drug interactions, and the development of fungal resistance. All the antifungal targets (existing and newer) and pipeline molecules showing promise against these targets are reviewed. The objective was to predict or repurpose phyto-based antifungal compounds based on a dual target inhibition approach (Sterol-14-α- demethylase and HSP-90) using a case study. In pursuit of repurposing the phytochemicals as antifungal agents, a team of researchers visited Aravalli Biodiversity Park (ABP), Delhi, India, to collect information on available medicinal plants. From 45 plants, a total of 1149 ligands were collected, and virtual screening was performed using Schrodinger Suite 2016 software to get 83 hits against both the target proteins: Sterol-14-α-demethylase and HSP-90. After analysis of docking results, ligands were selected based on their interaction against both the target proteins and comparison with respective standard ligands (fluconazole and ganetespib). We have selected Isocarthamidin, Quercetin and Boeravinone B based on their docking score and binding interaction against the HSP-90 (Docking Score -9.65, -9.22 and -9.21, respectively) and 14-α-demethylase (Docking Score -9.19, -10.76 and -9.74 respectively). The docking protocol was validated and MM/GBSA studies depicted better stability of selected three ligands (Isocarthamidin, Quercetin, Boeravinone B) complex as compared to standard complex. Further, MD simulation studies were performed using the Desmond (67) software package version 2018-4. All the findings are presented as a case study for the prediction of dual targets for the repurposing of certain phytochemicals as antifungal agents.