A One Health approach to overcoming fungal disease and antifungal resistance.

The global burden of fungal disease poses a substantial threat to human, animal, and environmental health, endangering both human and livestock populations and creating vulnerabilities to food supplies world-wide. Antifungal drugs provide essential therapies to humans and animals against infections, while fungicides provide protection in agriculture. However, a limited arsenal of antifungal agents results in cross-use between agriculture and health, promoting the development of resistance, and drastically reducing our defenses against disease. Critically, antifungal resistant strains found ubiquitously within the natural environment demonstrate resistance to the same classes of antifungals used to treat human and animal infections, hindering effective treatment within the clinic. This interconnectivity supports the need for a One Health approach to combat fungal diseases and overcome antifungal resistance, ensuring that treatment and protection of a defined group does not inadvertently endanger or sacrifice other plants, animals, or humans. In this review, we present sources of antifungal resistance and discuss the integration of environmental and clinical resources to manage disease. Moreover, we explore opportunities for drug synergy and repurposing strategies, highlight fungal targets being investigated to overcome resistance, and propose technologies for the discovery of novel fungal targets. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.

A central role for polyprenol reductase in plant dolichol biosynthesis.

Dolichol is an essential polyisoprenoid within the endoplasmic reticulum of all eukaryotes. It serves as a membrane bound anchor onto which N-glycans are assembled prior to being transferred to nascent polypeptides, many of which enter the secretory pathway. Historically, it has been posited that the accumulation of dolichol represents the 'rate-limiting' step in the evolutionary conserved process of N-glycosylation, which ultimately affects the efficacy of approximately one fifth of the entire eukaryotic proteome. Therefore, this study aimed to enhance dolichol accumulation by manipulating the enzymes involved in its biosynthesis using an established Nicotiana benthamiana platform. Co-expression of a Solanum lycopersicum (tomato) cis-prenyltransferase (CPT) and its cognate partner protein, CPT binding protein (CPTBP), that catalyze the antepenultimate step in dolichol biosynthesis led to a 400-fold increase in the levels of long-chain polyprenols but resulted in only modest increases in dolichol accumulation. However, when combined with a newly characterized tomato polyprenol reductase, dolichol biosynthesis was enhanced by approximately 20-fold. We provide further evidence that in the aquatic macrophyte, Lemna gibba, dolichol is derived exclusively from the mevalonic acid (MVA) pathway with little participation from the evolutionary co-adopted non-MVA pathway. Taken together these results indicate that to effectively enhance the in planta accumulation of dolichol, coordinated synthesis and reduction of polyprenol to dolichol, is strictly required.

Colorimetric Detection of Mercury(II) Ion in Aqueous Solution Using Silver Nanoparticles.

Novel green-chemistry synthesis of silver nanoparticles (AgNPs) is introduced as a low-cost, rapid and easy-to-use analytical method for mercury ion detection. Aqueous fruit extract of water apple (Syzygium aqueum) was used for the first time as bioreductant to synthesize stable AgNPs. The prepared AgNPs have a yellowish-brown color with a surface plasmon resonance peak at 420 nm. The addition of Hg(II) ions then changes the AgNPs color to colorless. The color change was in proportion to the concentration of Hg(II) ions. The presence of other metal ions in the system was also evaluated. The proposed method shows good selectivity and sensitivity towards Hg(II) ions. Using UV-visible spectrophotometry, the detection limit of the developed method was 8.5 × 10-7 M. The proposed method has been successfully applied for determination of Hg(II) ions in tap and lake water samples with precision better than 5%.