Candidalysin: An unlikely aide for fungal gut commensalism.

Fungi colonize the mammalian gastrointestinal (GI) tract and can adopt both commensal and opportunistic lifestyles. In a recent issue of Nature, Liang et al. unraveled the complex interplay between Candida morphotypes and the gut bacterial microbiota and described a key role for candidalysin in gut colonization.

High-Throughput Screening of the Repurposing Hub Library to Identify Drugs with Novel Inhibitory Activity against and Biofilms.

Candidiasis is one of the most frequent nosocomial infections affecting an increasing number of at-risk patients. remains the most frequent causative agent of candidiasis, but, in the last decade, has emerged as a formidable multi-drug-resistant pathogen. Both species are fully capable of forming biofilms, which contribute to resistance, increasing the urgency for new effective antifungal therapies.

Development of an Imaging Flow Cytometry Method for Fungal Cytological Profiling and Its Potential Application in Antifungal Drug Development.

Automated imaging techniques have been in increasing demand for the more advanced analysis and efficient characterization of cellular phenotypes. The success of the image-based profiling method hinges on assays that can rapidly and simultaneously capture a wide range of phenotypic features. We have developed an automated image acquisition method for fungal cytological profiling (FCP) using an imaging flow cytometer that can objectively measure over 250 features of a single fungal cell.

Screening the medicine for malaria venture's Pandemic Response Box to identify novel inhibitors of Candida albicans and Candida auris biofilm formation.

Candida spp. are opportunistic yeasts capable of forming biofilms, which contribute to resistance, increasing the urgency for new effective antifungal therapies. Repurposing existing drugs could significantly accelerate the development of novel therapies against candidiasis.

Antifungal therapy of biofilms: Past, present and future.

Virtually all species linked to clinical candidiasis are capable of forming highly resistant biofilms on different types of surfaces, which poses an additional significant threat and further complicates therapy of these infections. There is a scarcity of antifungal agents, and their effectiveness, particularly against biofilms, is limited. Here we provide a historical perspective on antifungal agents and therapy of biofilms.

A 384-Well Microtiter Plate Model for Candida Biofilm Formation and Its Application to High-Throughput Screening.

Candidiasis, infections caused by Candida spp., represents one of the most common nosocomial infections afflicting an expanding number of compromised patients. Antifungal therapeutic options are few and show limited efficacy.

Our current clinical understanding of Candida biofilms: where are we two decades on?

Clinically we have been aware of the concept of Candida biofilms for many decades, though perhaps without the formal designation. Just over 20 years ago the subject emerged on the back of progress made from the bacterial biofilms, and academic progress pace has continued to mirror the bacterial biofilm community, albeit at a decreased volume. It is apparent that Candida species have a considerable capacity to colonize surfaces and interfaces and form tenacious biofilm structures, either alone or in mixed species communities.

A Facile High-Throughput Model of Surface-Independent Staphylococcus aureus Biofilms by Spontaneous Aggregation.

Many microbes in their natural habitats are found in biofilm ecosystems attached to surfaces and not as free-floating (planktonic) organisms. Furthermore, it is estimated that nearly 80% of human infections are associated with biofilms. Biofilms are traditionally defined as three-dimensional, structured microbial communities that are attached to a surface and encased in a matrix of exopolymeric material.

Screening the CALIBR ReFRAME Library in Search for Inhibitors of Biofilm Formation.

is an emerging yeast which, since its first isolation about a decade ago, has spread rapidly and triggered major infectious outbreaks in health care facilities around the world. strains often display resistance to clinically-used antifungal agents, contributing to high mortality rates. Thus, there is an urgent need for new antifungals to contain the spread of this emerging multi-drug resistant pathogen and to improve patient outcomes.

Bismuth nanoparticles obtained by a facile synthesis method exhibit antimicrobial activity against and .

Background: Bismuth compounds are known for their activity against multiple microorganisms; yet, the antibiotic properties of bismuth nanoparticles (BiNPs) remain poorly explored. The objective of this work is to further the research of BiNPs for nanomedicine-related applications. Stable Polyvinylpyrrolidone (PVP)-coated BiNPs were produced by a chemical reduction process, in less than 30 min.

Inhibition of Mixed Biofilms of and Methicillin-Resistant by Positively Charged Silver Nanoparticles and Functionalized Silicone Elastomers.

Both bacterial and fungal organisms display the ability to form biofilms; however, mixed bacterial/fungal biofilms are particularly difficult to control and eradicate. The opportunistic microbial pathogens and are among the most frequent causative agents of healthcare-acquired infections, and are often co-isolated forming mixed biofilms, especially from contaminated catheters. These mixed species biofilms display a high level of antibiotic resistance; thus, these infections are challenging to treat resulting in excess morbidity and mortality.

Silver Nanoantibiotics Display Strong Antifungal Activity Against the Emergent Multidrug-Resistant Yeast Under Both Planktonic and Biofilm Growing Conditions.

is an emergent multidrug-resistant pathogenic yeast with an unprecedented ability for a fungal organism to easily spread between patients in clinical settings, leading to major outbreaks in healthcare facilities. The formation of biofilms by contributes to infection and its environmental persistence. Most antifungals and sanitizing procedures are not effective against , but antimicrobial nanomaterials could represent a viable alternative to combat the infections caused by this emerging pathogen.

Bismuth Nanoantibiotics Display Anticandidal Activity and Disrupt the Biofilm and Cell Morphology of the Emergent Pathogenic Yeast .

is an emergent multidrug-resistant pathogenic yeast, which forms biofilms resistant to antifungals, sanitizing procedures, and harsh environmental conditions. Antimicrobial nanomaterials represent an alternative to reduce the spread of pathogens-including yeasts-regardless of their drug-resistant profile. Here we have assessed the antimicrobial activity of easy-to-synthesize bismuth nanoparticles (BiNPs) against the emergent multidrug-resistant yeast , under both planktonic and biofilm growing conditions.

Current Antimycotics, New Prospects, and Future Approaches to Antifungal Therapy.

Fungal infections represent an increasing threat to a growing number of immune- and medically compromised patients. Fungi are eukaryotic organisms and, as such, there is a limited number of selective targets that can be exploited for antifungal drug development. This has also resulted in a very restricted number of antifungal drugs that are clinically available for the treatment of invasive fungal infections at the present time-polyenes, azoles, echinocandins, and flucytosine.

Screening Repurposing Libraries for Identification of Drugs with Novel Antifungal Activity.

Fungal organisms are ubiquitous in nature, and progress of modern medicine is creating an expanding number of severely compromised patients susceptible to a variety of opportunistic fungal infections. These infections are difficult to diagnose and treat, leading to high mortality rates. The limited antifungal arsenal, the toxicity of current antifungal drugs, the development of resistance, and the emergence of new multidrug-resistant fungi, all highlight the urgent need for new antifungal agents.

FDA Approved Drug Library Screening Identifies Robenidine as a Repositionable Antifungal.

Due to the increasing prevalence of pathogenic fungal infections, the emergence of antifungal resistant clinical isolates worldwide, and the limited arsenal of available antifungals, developing new antifungal strategies is imperative. In this study, we screened a library of 1068 FDA-approved drugs to identify hits that exhibit broad-spectrum antifungal activity. Robenidine, an anticoccidial agent which has been widely used to treat coccidian infections of poultry and rabbits, was identified in this screen.

Fast, facile synthesis method for BAL-mediated PVP-bismuth nanoparticles.

Bismuth is a water-insoluble non-toxic metallic element used in a wide array of pharmaceutical products, cosmetics, and catalysts, among others. Yet, the research regarding the use of bismuth nanoparticles (BiNPs) for antimicrobial treatments is scarce. Most of the current protocols for synthesizing BiNPs suitable for medical uses cannot be easily replicated in non-specialized laboratories.

CARD9-Associated Dectin-1 and Dectin-2 Are Required for Protective Immunity of a Multivalent Vaccine against Infection.

species are fungal pathogens that can cause a widely varied clinical manifestation from mild pulmonary symptom to disseminated, life-threatening disease. We have previously created a subunit vaccine by encapsulating a recombinant coccidioidal Ag (rCpa1) in glucan-chitin particles (GCPs) as an adjuvant-delivery system. The GCP-rCpa1 vaccine has shown to elicit a mixed Th1 and Th17 response and confers protection against pulmonary coccidioidomycosis in mice.

Inhibition of Biofilm Formation on Medical and Environmental Surfaces by Silver Nanoparticles.

is an emerging pathogenic fungus implicated in healthcare-associated outbreaks and causes bloodstream infections associated with high mortality rates. Biofilm formation represents one of the major pathogenetic traits associated with this microorganism. Unlike most other species, has the ability to survive for weeks on different surfaces.

Activating a Silver Lipoate Nanocluster with a Penicillin Backbone Induces a Synergistic Effect against Biofilm.

Many antibiotic resistances to penicillin have been reported, making them obsolete against multiresistant bacteria. Because penicillins act by inhibiting cell wall production while silver particles disrupt the cell wall directly, a synergetic effect is anticipated when both modes of action are incorporated into a cluster. To test this hypothesis, the lipoate ligands (LA) of a silver cluster (Ag) of known composition (AgLA) were covalently conjugated to 6-aminopenicillanic acid, a molecule with a β-lactam backbone.

Antifungal Activity of a Hydroethanolic Extract From Leaves Against and .

We have previously reported on the activity of different extracts from sp. against , with the hydroethanolic extract prepared from leaves of , an arboreal species widely distributed in arid environments of South America and often used in folk medicine, displaying the highest activity. Here we have further evaluated the antifungal activity of this extract against strains of and , the two most common etiological agents of candidiasis.

Protocol optimization for a fast, simple and economical chemical reduction synthesis of antimicrobial silver nanoparticles in non-specialized facilities.

Objective: Silver nanoparticles (AgNPs) can be difficult or expensive to obtain or synthesize for laboratories in resource-limited facilities. The purpose of this work was to optimize a synthesis method for a fast, facile, and cost-effective synthesis of AgNPs with antimicrobial activity, which can be readily implemented in non-specialized facilities and laboratories.

Results: The optimized method uses a rather simple and rapid chemical reduction process that involves the addition of a polyvinylpyrrolidone solution to a warmed silver nitrate solution under constant vigorous stirring, immediately followed by the addition of sodium borohydride.

Filamentation Is Associated with Reduced Pathogenicity of Multiple Non- Species.

Candidiasis affects a wide variety of immunocompromised and medically compromised patients. , a major human fungal pathogen, accounts for about 50% of all cases, while the remainder are caused by the less pathogenic non- species (NACS). These species are believed to be less pathogenic, in part, because they do not filament as readily or robustly as , although definitive evidence is lacking.

Repositionable Compounds with Antifungal Activity against Multidrug Resistant Identified in the Medicines for Malaria Venture's Pathogen Box.

Unlabelled: Background has spread rapidly around the world as a causative agent of invasive candidiasis in health care facilities and there is an urgent need to find new options for treating this emerging, often multidrug-resistant pathogen.

Methods: We screened the Pathogen Box® chemical library for inhibitors of strain 0390, both under planktonic and biofilm growing conditions.

Results: The primary screen identified 12 compounds that inhibited at least 60% of biofilm formation or planktonic growth.