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 .

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).

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.

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.

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 .

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.

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.

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.

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.

Nitric oxide-loaded nano- and microparticle platforms serving as potential new antifungal therapeutics.

Fungal diseases are a leading threat to human health, especially in individuals with compromised immunity. Although there have been recent important advances in antifungal drug development, antifungal resistance, drug-drug interactions and difficulties in delivery remain major challenges. Among its pleiotropic actions, nitric oxide (NO) is a key molecule in host defense.

Melanization of Is Associated with Alteration of Extracellular pH.

is a recently emerged global fungal pathogen, which causes life-threatening infections, often in healthcare settings. infections are worrisome because the fungus is often resistant to multiple antifungal drug classes. Furthermore, forms durable and difficult to remove biofilms.

Caspofungin Affects Extracellular Vesicle Production and Cargo in .

Antifungal resistance has become more frequent, either due to the emergence of naturally resistant species or the development of mechanisms that lead to resistance in previously susceptible species. Among these fungal species of global threat, stands out for commonly being highly resistant to antifungal drugs, and some isolates are pan-resistant. The rate of mortality linked to infections varies from 28% to 78%.

Pathogenicity & virulence of - A multifaceted organism adapted to intracellular environments.

Histoplasmosis is a systemic mycosis caused by the thermally dimorphic fungus . Although healthy individuals can develop histoplasmosis, the disease is particularly life-threatening in immunocompromised patients, with a wide range of clinical manifestations depending on the inoculum and virulence of the infecting strain. In this review, we discuss the established virulence factors and pathogenesis traits that make highly adapted to a wide variety of hosts, including mammals.

Isolation of Extracellular Vesicles from Candida auris.

Extracellular vesicles (EVs) are structures released by a variety of cells from all kingdoms of life. EVs are typically involved in communication between tissues and organs, between distinct organisms, or inside microbial communities. The plasticity of these structures is reflected in the range of biological effects they are able to induce or inhibit.

Extracellular Vesicles Regulate Biofilm Formation and Yeast-to-Hypha Differentiation in Candida albicans.

In this study, we investigated the influence of fungal extracellular vesicles (EVs) during biofilm formation and morphogenesis in Candida albicans. Using crystal violet staining and scanning electron microscopy (SEM), we demonstrated that C. albicans EVs inhibited biofilm formation .

Methamphetamine Enhances Cryptococcus neoformans Melanization, Antifungal Resistance, and Pathogenesis in a Murine Model of Drug Administration and Systemic Infection.

Methamphetamine (METH) is a major public health and safety problem in the United States. Chronic METH abuse is associated with a 2-fold-higher risk of HIV infection and, possibly, additional infections, particularly those that enter through the respiratory tract or skin. Cryptococcus neoformans is an encapsulated opportunistic yeast-like fungus that is a relatively frequent cause of meningoencephalitis in immunocompromised patients, especially in individuals with AIDS.

Replicative Aging Remodels the Cell Wall and Is Associated with Increased Intracellular Trafficking in Human Pathogenic Yeasts.

Replicative aging is an underexplored field of research in medical mycology. Cryptococcus neoformans () and Candida glabrata () are dreaded fungal pathogens that cause fatal invasive infections. The fungal cell wall is essential for yeast viability and pathogenesis.

Lessons Learned from Studying Histoplasma capsulatum Extracellular Vesicles.

Histoplasma capsulatum is a major endemic mycosis. Our laboratories have demonstrated that H. capsulatum produces extracellular vesicles (EV) that are loaded with diverse compounds that influence virulence.

Cellular and Extracellular Vesicle RNA Analysis in the Global Threat Fungus .

Emerging and reemerging pathogens are a worldwide concern, and it is predicted that these microbes will cause severe outbreaks. Candida auris affects people with weakened immune systems, particularly those who are hospitalized or are in health care facilities. Extracellular vesicles (EVs) are lipid bilayer structures released by organisms from all domains of life.

A Histoplasma capsulatum Lipid Metabolic Map Identifies Antifungal Targets.

Lipids play a fundamental role in fungal cell biology, being essential cell membrane components and major targets of antifungal drugs. A deeper knowledge of lipid metabolism is key for developing new drugs and a better understanding of fungal pathogenesis. Here, we built a comprehensive map of the Histoplasma capsulatum lipid metabolic pathway by incorporating proteomic and lipidomic analyses.

Transcriptional and translational landscape of in response to caspofungin.

has emerged as a serious worldwide threat by causing opportunistic infections that are frequently resistant to one or more conventional antifungal medications resulting in high mortality rates. Against this backdrop, health warnings around the world have focused efforts on understanding fungal biology and effective prevention and treatment approaches to combat this fungus. To date, there is little information about the differentially expressed genes when this fungus is treated with conventional antifungals, and caspofungin is a standard echinocandin deployed in the therapy against .

Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris.

Candida auris is a recently described multidrug-resistant pathogenic fungus that is increasingly responsible for health care-associated outbreaks across the world. Bloodstream infections of this fungus cause death in up to 70% of cases. Aggravating this scenario, the disease-promoting mechanisms of C.