Nitric Oxide-Releasing Microparticles: A Novel Treatment for Onychomycosis.

Onychomycosis is one of the most prevalent fungal infections worldwide, resulting in negative effects on general quality of life. Management of the disease encounters a series of obstacles, and antifungal treatment has a low success rate. We aimed to develop and evaluate a novel formulation of NO-releasing microparticles (SNO-MPs) against some of the most common causative agents of onychomycosis: , , , and .

Assessing Medical Student Competency in Community-Engaged Service Learning: Development and Validity Evidence of a Multisource Feedback Tool.

Purpose: Community-engaged service learning (CSL) fosters partnerships to address health disparities and instills cultural humility and social responsibility in medical students. Despite its increasing integration into medical education, learner assessment remains a challenge; most assessments include reflection or participation but overlook behavioral and attitudinal skills. The authors aimed to cocreate a multisource feedback tool to assess observable competencies during the experiential phase of CSL.

Extracellular vesicles from Distinct Strains Modulate Phagocyte Function and Promote Fungal Persistence.

Fungal extracellular vesicles (EVs) are lipid-bilayer compartments that transport a wide range of molecules, including proteins, polysaccharides, pigments, small metabolites, lipids, and RNA. In fungal pathogens, EVs harbor virulence factors as well as antigenic determinants that modulate the host immune response. In this work, we investigated the modulatory effects of EVs released by two phenotypically and genotypically distinct strains of (G-217B and G-184A) on bone marrow-derived macrophages (BMDMs) and bone marrow-derived dendritic cells (BMDCs).

An overview of rapid non-culture-based techniques in various clinical specimens for the laboratory diagnosis of .

() is a temperature-dependent biphasic deep opportunistic infectious fungus that primarily affects individuals with advanced HIV disease and other immunocompromised populations. Traditional diagnostic methods rely on fungal culture, but this process, although sensitive, is time-consuming and susceptible to contamination. Therefore, non-culture techniques serve as important complementary and alternative methods for diagnosing talaromycosis.

Extracellular vesicles from diverse fungal pathogens induce species-specific and endocytosis-dependent immunomodulation.

Microbial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. Microbial EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that EVs secreted by Candida albicans trigger type I interferon signaling in host cells specifically via the cGAS-STING innate immune signaling pathway.

In Vitro Evidence for the Efficacy of Manuka Honey and Its Components Against the Major Human Pathogenic Species.

: While various clinical manifestations occur in sporotrichosis, cutaneous forms predominate. The recommended sporotrichosis treatment is itraconazole, an antifungal with certain restrictions. In recent years, the observation of reduced treatment effectiveness in some patients has arisen, possibly due to spp.

Characterizing extracellular vesicles of human fungal pathogens.

Since their discovery in 2007, there has been growing awareness of the importance of fungal extracellular vesicles (EVs) for fungal physiology, host-pathogen interactions and virulence. Fungal EVs are nanostructures comprising bilayered membranes and molecules of various types that participate in several pathophysiological processes in fungal biology, including secretion, cellular communication, immunopathogenesis and drug resistance. However, many questions remain regarding the classification of EVs, their cellular origin, passage across the cell wall, experimental models for functional and compositional analyses, production in vitro and in vivo and biomarkers for EVs.

Reduced growth and biofilm formation at high temperatures contribute to Cryptococcus deneoformans dermatotropism.

Cryptococcus deneoformans (Cd) and C. neoformans (Cn) differ in geographic prevalence and dermatotropism, with Cd strains more commonly isolated from temperate regions and skin infections. Rising global temperatures prompt concerns regarding selection for environmental fungal species with increased thermotolerance, as high mammalian temperatures provide protection against many fungal species.

as an Invertebrate Model for Studying Fungal Infections.

The incidence of fungal infections continues to increase and one of the factors responsible for these high rates is the emergence of multi-resistant species, hospitalizations, inappropriate or prolonged use of medications, and pandemics, such as the ongoing HIV/AIDS pandemic. The recent pandemic caused by the severe acute respiratory syndrome virus (SARS-CoV-2) has led to a significant increase in fungal infections, especially systemic mycoses caused by opportunistic fungi. There is a growing and urgent need to better understand how these microorganisms cause infection and develop resistance as well as to develop new therapeutic strategies to combat the diverse diseases caused by fungi.

Fungal Metabolomics: A Comprehensive Approach to Understanding Pathogenesis in Humans and Identifying Potential Therapeutics.

Metabolomics has emerged as a transformative tool in the study of microbes, including pathogenic fungi, facilitating the identification of unique metabolic profiles that elucidate their pathogenic mechanisms, host interactions, and treatment resistance. This review highlights key applications of metabolomics in understanding fungal metabolites essential for human virulence, such as mycotoxins produced by various fungal species, including (gliotoxin, fumagillins) and species (phenylethyl alcohol, TCA cycle metabolites), and secondary metabolites that contribute to pathogenicity. It also explores the metabolic adaptations of fungi in relation to drug resistance and biofilm formation, revealing alterations in key metabolic pathways during infection, as seen in and .

mGem: A quarter century with the Pirofski-Casadevall damage response framework-a dynamic construct for understanding microbial pathogenesis.

A quarter of a century ago, Liise-anne Pirofski and Arturo Casadevall shared their concepts of microbial pathogenesis through the lens of a damage-response framework (DRF), which characterizes disease by assessing the dynamic interactions between the host and pathogen as reflected by damage as the readout. This framework has evolved to be a powerful tool for understanding the biology of complex infectious diseases, analyzing emerging and reemerging microbes, and developing therapeutic approaches to combat infections. The DRF is also frequently used to explain research at scientific meetings and to teach microbial pathogenesis to diverse learners.

Extracellular vesicles from diverse fungal pathogens induce species-specific and endocytosis-dependent immunomodulation.

Microbial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. Microbial EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that EVs secreted by trigger type I interferon signaling in host cells specifically via the cGAS-STING innate immune signaling pathway.

Interactions of the emerging fungus with reveal phenotypic changes with direct implications on the response to stress and virulence.

Unlabelled: is an emerging fungal pathogen notable for its resistance to multiple antifungals and ability to survive in various environments. Understanding the interactions between and environmental protozoa, such as could provide insights into fungal adaptability and pathogenicity. Two isolates (MMC1 and MMC2) were co-cultured with to examine interaction dynamics, survival, stress responses, growth, virulence, biofilm formation, and antifungal susceptibility.

The biofilm produced by Cryptococcus neoformans protects the fungus from the antifungal and anti-melanin effects of cyclosporine.

Understanding Cryptococcus neoformans pathogenesis requires a detailed analysis of the various virulence factors that contribute to its ability to cause disease. Cyclosporine, calcineurin inhibitor, impairs C. neoformans production of a polysaccharide capsule and secretion of urease, which are critical for cryptococcal pathogenesis.

Alkaloids solenopsins from fire ants display and activity against the yeast .

The urgency surrounding as a public health threat is highlighted by both the Center for Disease Control (CDC) and World Health Organization (WHO) that categorized this species as a priority fungal pathogen. Given the current limitations of antifungal therapy for , particularly due to its multiple resistance to the current antifungals, the identification of new drugs is of paramount importance. Some alkaloids abundant in the venom of the red invasive fire ant (), known as solenopsins, have garnered attention as potent inhibitors of bacterial biofilms, and there are no studies demonstrating such effects against fungal pathogens.

The microbial damage and host response framework: lesson learned from pathogenic survival trajectories and immunoinflammatory responses of infection.

The adverse outcomes of fungal infection in mammalian hosts depend on the complex interactions between the host immune system and pathogen virulence-associated traits. The main clinical problems arise when the host response is either too weak to effectively eliminate the pathogen or overly aggressive, resulting in host tissue damage rather than protection. This article will highlight current knowledge regarding the virulence attributions and mechanisms involved in the dual-sided role of the host immune system in the immunopathogenesis of the thermally dimorphic fungus through the lens of the damage response framework (DRF) of microbial pathogenesis model.

Diagnostic Performances of an in-House Immunochromatography Test Based on the Monoclonal Antibody 18B7 to Glucuronoxylomannan for Clinical Suspected Cryptococcosis: a Large-Scale Prototype Evaluation in Northern Thailand.

Objective: Cryptococcosis predominantly presents as a meningoencephalitis in Thailand. Early and expeditious diagnosis is essential for reducing both mortality and morbidity associated with cryptococcal meningitis. We aim to define and establish the diagnostic performances between the benchmark commercially available diagnostic kit (CrAg® LFA) and the large-scale prototype of an inexpensive in-house immunochromatographic test (ICT) based on monoclonal antibody (MAb) 18B7.

The yeast genus Tardiomyces gen. nov. with one new species and two new combinations.

Purpose: Rare yeasts species are increasingly reported as causative agents of invasive human infection. Proper identification and antifungal therapy are essential to manage these infections. Candida blankii is one of these emerging pathogens and is known for its reduced susceptibility to multiple antifungals.

Adaptation to an amoeba host drives selection of virulence-associated traits and genetic variation in saprotrophic .

Amoebae are micropredators that play an important role in controlling fungal populations in ecosystems. However, the interaction between fungi and their amoebic predators suggests that the pressure from predatory selection can significantly influence the development of fungal virulence and evolutionary processes. Thus, the purpose of this study was to investigate the adaptation of saprotrophic strains during their interactions with .

Candida albicans extracellular vesicles trigger type I IFN signalling via cGAS and STING.

The host type I interferon (IFN) pathway is a major signature of inflammation induced by the human fungal pathogen, Candida albicans. However, the molecular mechanism for activating this pathway in the host defence against C. albicans remains unknown.

Acquired Triazole Resistance Alters Pathogenicity-Associated Features in in an Isolate-Dependent Manner.

Fluconazole resistance is commonly encountered in , and the yeast frequently displays resistance to other standard drugs, which severely limits the number of effective therapeutic agents against this emerging pathogen. In this study, we aimed to investigate the effect of acquired azole resistance on the viability, stress response, and virulence of this species. Fluconazole-, posaconazole-, and voriconazole- resistant strains were generated from two susceptible clinical isolates (0381, 0387) and compared under various conditions.

Traversing the Cell Wall: The Chitinolytic Activity of Extracellular Vesicles Facilitates Their Release.

is the causative agent of histoplasmosis. Treating this fungal infection conventionally has significant limitations, prompting the search for alternative therapies. In this context, fungal extracellular vesicles (EVs) hold relevant potential as both therapeutic agents and targets for the treatment of fungal infections.

Vaccine development for pathogenic fungi: current status and future directions.

Introduction: Fungal infections are caused by a broad range of pathogenic fungi that are found worldwide with different geographic distributions, incidences, and mortality rates. Considering that there are relatively few approved medications available for combating fungal diseases and no vaccine formulation commercially available, multiple groups are searching for new antifungal drugs, examining drugs for repurposing and developing antifungal vaccines, in order to control deaths, sequels, and the spread of these complex infections.

Areas Covered: This review provides a summary of advances in fungal vaccine studies and the different approaches under development, such as subunit vaccines, whole organism vaccines, and DNA vaccines, as well as studies that optimize the use of adjuvants.