Clinical characteristics and outcomes of colonization and infection by yeast species in solid organ transplant recipients: Molecular identification and antifungal susceptibility patterns of isolates.

Fungal infections are serious complications after solid organ transplantation, with high mortality and morbidity. Given the importance of the local epidemiological data and also extensive prophylactic regimens in solid organ transplant (SOT) recipients, this study aimed to investigate the clinical characteristics and resistance patterns of yeast isolates in SOT recipients at a main referral transplant center in Iran. Of the 275 recipients enrolled, 22 (8%) had at least one positive yeast culture at a median of 5 days after transplantation.

Single-cell quantitative bioimaging of liver stage translation.

parasites cause malaria in humans. New multistage active antimalarial drugs are needed, and a promising class of drugs targets the core cellular process of translation, which has many potential molecular targets. During the obligate liver stage, parasites grow in metabolically active hepatocytes, making it challenging to study core cellular processes common to both host cells and parasites, as the signal from the host typically overwhelms that of the parasite.

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.

Single-cell quantitative bioimaging of liver stage translation.

parasite resistance to existing antimalarial drugs poses a devastating threat to the lives of many who depend on their efficacy. New antimalarial drugs and novel drug targets are in critical need, along with novel assays to accelerate their identification. Given the essentiality of protein synthesis throughout the complex parasite lifecycle, translation inhibitors are a promising drug class, capable of targeting the disease-causing blood stage of infection, as well as the asymptomatic liver stage, a crucial target for prophylaxis.

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.

Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites.

Gene expression in malaria parasites is subject to various layers of regulation, including histone post-translational modifications (PTMs). Gene regulatory mechanisms have been extensively studied during the main developmental stages of Plasmodium parasites inside erythrocytes, from the ring stage following invasion to the schizont stage leading up to egress. However, gene regulation in merozoites that mediate the transition from one host cell to the next is an understudied area of parasite biology.

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.

Design, synthesis and biological activity of hybrid antifungals derived from fluconazole and mebendazole.

A novel series of triazole alcohol antifungals bearing a 5-benzoylbenzimidazol-2-ylthio side chain have been designed and synthesized as hybrids of fluconazole (a typical triazole antifungal) and mebendazole (an anthelmintic agent with antifungal activity). The title compounds were synthesized via the reaction of an appropriate oxirane and desired 2-mercaptobenzimidazole. Although there was possibility for formation of different N-substituted or S-substituted products, the structures of final compounds were assigned as thioether congeners by using C NMR spectroscopy.

Design of proteasome inhibitors with oral efficacy in vivo against and selectivity over the human proteasome.

The proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates that are potent and specific inhibitors of the 20S proteasome (20S) β5 active site and that exhibit fast-acting antimalarial activity. They selectively inhibit the growth of compared with a human cell line and exhibit high potency against field isolates of and They have a low propensity for development of resistance and possess liver stage and transmission-blocking activity.

Lipid Secretion by Parasitic Cells of Contributes to Disseminated Disease.

is a soil-borne fungal pathogen and causative agent of a human respiratory disease (coccidioidomycosis) endemic to semi-desert regions of southwestern United States, Mexico, Central and South America. Aerosolized arthroconidia inhaled by the mammalian host first undergo conversion to large parasitic cells (spherules, 80-100 μm diameter) followed by endosporulation, a process by which the contents of spherules give rise to multiple endospores. The latter are released upon rupture of the maternal spherules and establish new foci of lung infection.

Coxiella burnetii and Related Tick Endosymbionts Evolved from Pathogenic Ancestors.

Both symbiotic and pathogenic bacteria in the family Coxiellaceae cause morbidity and mortality in humans and animals. For instance, Coxiella-like endosymbionts (CLEs) improve the reproductive success of ticks-a major disease vector, while Coxiella burnetii causes human Q fever, and uncharacterized coxiellae infect both animals and humans. To better understand the evolution of pathogenesis and symbiosis in this group of intracellular bacteria, we sequenced the genome of a CLE present in the soft tick Ornithodoros amblus (CLEOA) and compared it to the genomes of other bacteria in the order Legionellales.

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.

Molecular Effects of Silver Nanoparticles on Monogenean Parasites: Lessons from .

The mechanisms of action of silver nanoparticles (AgNPs) in monogenean parasites of the genus were investigated through a microarray hybridization approach using genomic information from the nematode . The effects of two concentrations of AgNPs were explored, low (6 µg/L Ag) and high (36 µg/L Ag). Microarray analysis revealed that both concentrations of AgNPs activated similar biological processes, although by different mechanisms.

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.

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.

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.

Candida albicans biofilm growth and dispersal: contributions to pathogenesis.

The fungal species Candida albicans is most frequently associated with biofilm formation in immune-compromised and medically compromised patients, and it is now firmly established that biofilm formation represents a major virulence factor during candidiasis. A growing body of evidence has demonstrated that C. albicans biofilm development is a highly regulated and coordinated process, where adhesive interactions, morphogenetic conversions, and consortial behavior play significant roles.