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Neuromeningeal cryptococcosis (NMC) is a life-threatening opportunistic infection in advanced HIV disease patients (AHDP). It is caused by Cryptococcus spp. complexes and mainly occurs in sub-Saharan Africa. In this study, we performed molecular characterization and antifungal susceptibility profiling of Cryptococcus isolates from AHDP in Kinshasa (DRC). Additionally, we investigated a possible association between NMC severity factors and the Cryptococcus neoformans ( Cn ) multilocus sequence typing (MLST) profiles. We characterized the isolates using PCR serotyping, MALDI-TOF MS, internal transcribed spacer (ITS) sequencing, and MLST. Susceptibility testing for the major antifungal drugs was performed according to the EUCAST guidelines. Parameters associated with NMC severity, such as hypoglycorrhachia (< 50 mg/dL), increased cerebral spinal fluid opening pressure (> 30 cm H 2 O), and poor therapeutic outcome were compared with the Cn MLST sequences type (ST). Twenty-three out of 29 Cryptococcus isolates were identified as serotype A using PCR serotyping (79.3%; 95% IC: 65.5–93.1), while six (20.7%; 95% IC: 6.9–34.5) were not serotypable. The 29 isolates were identified by ITS sequencing as follows: Cryptococcus neoformans (23/29, 79.3%), Cutaneotrichosporon curvatus ( previously called Cryptococcus curvatus) (5/29, 17.2%), and Papiliotrema laurentii ( Cryptococcus laurentii ) (1/29, 3.5%). Using the ISHAM MLST scheme, all Cn isolates were identified as molecular type VNI. These comprised seven different STs: ST93 (n = 15), ST5 (n = 2), ST53 (n = 1), ST31 (n = 1), ST4 (n = 1), ST69 (n = 1), and one novel ST that has not yet been reported from other parts of the world and was subsequently assigned as ST659 (n = 2). Of the included strains, only Papiliotrema laurentii was resistant to amphoterin B (1/29, 3.5%), 6.8% (2/29) were resistant to 5-flucytosine (the single Papiliotrema laurentii strain and one Cryptococcus neoformans isolate), and 13.8% (4/29) to fluconazole, including two of five (40%) Cutaneotrichosporon curvatus and two of 23 (8.7%) C . neoformans strains. We found a significative association between poor therapeutic outcome and a non-ST93 sequence type of causative strains (these concerned the less common sequence types: ST53, ST31, ST5, ST4, ST659, and ST69) (87.5% versus 40%, p = 0.02). Molecular analysis of Cryptococcus spp. isolates showed a wide species diversity and genetic heterogenicity of Cn within the VNI molecular type. Furthermore, it is worrying that among included strains we found resistances to several of the commonly used antifungals.

New Candida species such as Candida auris have emerged recently as important invasive fungal diseases. We report a case of C. bovina bloodstream infection in a 94-year-old patient in France. The species led to identification issues because it was misidentified by phenotypic and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry methods.

The pathogenic yeast Candida glabrata is intrinsically resilient to azoles and rapidly acquires resistance to these antifungals, in vitro and in vivo. In most cases azole-resistant C. glabrata clinical strains encode hyperactive CgPdr1 variants, however, resistant strains encoding wild-type CgPDR1 alleles have also been isolated, although remaining to be disclosed the underlying resistance mechanism. In this study, we scrutinized the mechanisms underlying resistance to azoles of 8 resistant clinical C. glabrata strains, identified along the course of epidemiological surveys undertaken in Portugal. Seven of the strains were found to encode CgPdr1 gain-of-function variants (I392M, E555K, G558C, and I803T) with the substitutions I392M and I803T being herein characterized as hyper-activating mutations for the first time. While cells expressing the wild-type CgPDR1 allele required the mediator subunit Gal11A to enhance tolerance to fluconazole, this was dispensable for cells expressing the I803T variant indicating that the CgPdr1 interactome is shaped by different gain-of-function substitutions. Genomic and transcriptomic profiling of the sole azole-resistant C. glabrata isolate encoding a wild-type CgPDR1 allele (ISTB218) revealed that under fluconazole stress this strain over-expresses various genes described to provide protection against this antifungal, while also showing reduced expression of genes described to increase sensitivity to these drugs. The overall role in driving the azole-resistance phenotype of the ISTB218 C. glabrata isolate played by these changes in the transcriptome and genome of the ISTB218 isolate are discussed shedding light into mechanisms of resistance that go beyond the CgPdr1-signalling pathway and that may alone, or in combination, pave the way for the acquisition of resistance to azoles in vivo.

Flavonoids are phytochemical compounds present in many plants, fruits, vegetables, and leaves, with potential applications in medicinal chemistry. Flavonoids possess a number of medicinal benefits, including anticancer, antioxidant, anti-inflammatory, and antiviral properties. They also have neuroprotective and cardio-protective effects. These biological activities depend upon the type of flavonoid, its (possible) mode of action, and its bioavailability. These cost-effective medicinal components have significant biological activities, and their effectiveness has been proved for a variety of diseases. The most recent work is focused on their isolation, synthesis of their analogs, and their effects on human health using a variety of techniques and animal models. Thousands of flavonoids have been successfully isolated, and this number increases steadily. We have therefore made an effort to summarize the isolated flavonoids with useful activities in order to gain a better understanding of their effects on human health.

Host defence peptides (HDPs) are integral components of innate immunity across all living organisms. These peptides can exert direct antibacterial effects, targeting planktonic cells (referred to as antimicrobial peptides), and exhibit antibiofilm (referred to as antibiofilm peptides), antiviral, antifungal and host-directed immunomodulatory activities. In this Review, we discuss how the complex functional attributes of HDPs provide many opportunities for the development of antimicrobial therapeutics, focusing particularly on their emerging antibiofilm properties. The mechanisms of action of antibiofilm peptides are compared and contrasted with those of antimicrobial peptides. Furthermore, obstacles for the practical translation of candidate peptides into therapeutics and the potential solutions are discussed. Critically, HDPs have the value-added assets of complex functional attributes, particularly antibiofilm and anti-inflammatory activities and their synergy with conventional antibiotics.In this Review, Hancock, Alford and Haney discuss how the complex functional attributes of host defence peptides provide many opportunities for the development of antimicrobial therapeutics, focusing on their emerging antibiofilm properties.

The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug–drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.

Invasive fungal infections pose an important threat to public health and are an under-recognized component of antimicrobial resistance, an emerging crisis worldwide. Across a period of profound global environmental change and expanding at-risk populations, human-infecting pathogenic fungi are evolving resistance to all licensed systemic antifungal drugs. In this Review, we highlight the main mechanisms of antifungal resistance and explore the similarities and differences between bacterial and fungal resistance to antimicrobial control. We discuss the research and innovation topics that are needed for risk reduction strategies aimed at minimizing the emergence of resistance in pathogenic fungi. These topics include links between the environment and One Health, surveillance, diagnostics, routes of transmission, novel therapeutics and methods to mitigate hotspots for fungal adaptation. We emphasize the global efforts required to steward our existing antifungal armamentarium, and to direct the research and development of future therapies and interventions.The impacts of fungal infections on human health are of increasing concern, and resistance of pathogenic fungi to all licensed systemic antifungals has been documented. In this Review, Fisher, Verweij and colleagues discuss the research and innovation topics that are needed to understand and minimize the occurrence and impact of antifungal resistance.

The interest in using natural antimicrobials instead of chemical preservatives in food products has been increasing in recent years. In regard to this, essential oils—natural and liquid secondary plant metabolites—are gaining importance for their use in the protection of foods, since they are accepted as safe and healthy. Although research studies indicate that the antibacterial and antioxidant activities of essential oils (EOs) are more common compared to other biological activities, specific concerns have led scientists to investigate the areas that are still in need of research. To the best of our knowledge, there is no review paper in which antifungal and especially antimycotoxigenic effects are compiled. Further, the low stability of essential oils under environmental conditions such as temperature and light has forced scientists to develop and use recent approaches such as encapsulation, coating, use in edible films, etc. This review provides an overview of the current literature on essential oils mainly on antifungal and antimycotoxigenic but also their antibacterial and antioxidant activities. Additionally, the recent applications of EOs including encapsulation, edible coatings, and active packaging are outlined.

Thiazole, a five-membered heteroaromatic ring, is an important scaffold of a large number of synthetic compounds. Its diverse pharmacological activity is reflected in many clinically approved thiazole-containing molecules, with an extensive range of biological activities, such as antibacterial, antifungal, antiviral, antihelmintic, antitumor, and anti-inflammatory effects. Due to its significance in the field of medicinal chemistry, numerous biologically active thiazole and bisthiazole derivatives have been reported in the scientific literature. The current review provides an overview of different methods for the synthesis of thiazole and bisthiazole derivatives and describes various compounds bearing a thiazole and bisthiazole moiety possessing antibacterial, antifungal, antiprotozoal, and antitumor activity, encouraging further research on the discovery of thiazole-containing drugs.

Due to the increasing demand for eco-friendly, cost-effective and safe technologies, biosynthetic metal nanoparticles have attracted worldwide attention. In this study, silver nanoparticles (AgNPs) were extracellularly biosynthesized using the culture supernatants of Aspergillus sydowii . During synthesis, color change was preliminarily judge of the generation of AgNPs, and the UV absorption peak at 420 nm further confirms the production of AgNPs. Transmission electron microscopy and X-ray diffraction were also used to identify the AgNPs. The results shows that AgNPs has crystalline cubic feature and is a polydisperse spherical particle with size between 1 and 24 nm. Three main synthesis factors (temperature, pH and substrate concentration) were optimized, the best synthesis conditions were as follows 50 °C, 8.0 and 1.5 mM. In the biological application of AgNPs, it shows effective antifungal activity against many clinical pathogenic fungi and antiproliferative activity to HeLa cells and MCF-7 cells in vitro. Our research finds a new path to biosynthesis of AgNPs in an eco-friendly manner, and bring opportunity for biomedical applications in clinic.