The sulfur-related metabolic status of during infection reveals cytosolic serine hydroxymethyltransferase as a promising antifungal target.

Sulfur metabolism is an essential aspect of fungal physiology and pathogenicity. Fungal sulfur metabolism comprises anabolic and catabolic routes that are not well conserved in mammals, therefore is considered a promising source of prospective novel antifungal targets. To gain insight into sulfur-related metabolism during infection, we used a NanoString custom nCounter-TagSet and compared the expression of 68 key metabolic genes in different murine models of invasive pulmonary aspergillosis, at 3 time-points, and under a variety of conditions.

Real-Time Changes in the Comfort of a Toric, Monthly, Soft Contact Lens Over a Long Day of Wear.

Purpose: The purpose of this work was to determine the comfort performance of a toric, monthly, silicon hydrogel CL (lehfilcon A; TOTAL30 for Astigmatism) over a long day of wear.

Methods: This was a 1-month, 3-visit, prospective, single-arm study. Adult, 18- to 45-year-old CL wearers with good vision who were minimally symptomatic (CLDEQ-8 scores ≤12) were enrolled.

Mycobiome analyses of critically ill COVID-19 patients.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a life-threatening complication in patients with severe COVID-19. Previously, acute respiratory distress syndrome in patients with COVID-19 has been associated with lung fungal dysbiosis, evidenced by reduced microbial diversity and colonization. Increased fungal burden in the lungs of critically ill COVID-19 patients is linked to prolonged mechanical ventilation and increased mortality.

Elevated mutation rates in multi-azole resistant Aspergillus fumigatus drive rapid evolution of antifungal resistance.

The environmental use of azole fungicides has led to selective sweeps across multiple loci in the Aspergillus fumigatus genome causing the rapid global expansion of a genetically distinct cluster of resistant genotypes. Isolates within this cluster are also more likely to be resistant to agricultural antifungals with unrelated modes of action. Here we show that this cluster is not only multi-azole resistant but has increased propensity to develop resistance to next generation antifungals because of variants in the DNA mismatch repair system.

A microscopy-based image analysis pipeline for the quantification of germination of filamentous fungi.

Germination is the fundamental process whereby fungi transition from the dormant and stress resistant spores into actively replicating cells such as hyphae. Germination is essential for fungal colonization of new environments and pathogenesis, yet this differentiation process remains relatively poorly understood. For filamentous fungi, the study of germination has been limited by the lack of high-throughput, temporal, low cost, and easy-to-use methods of quantifying germination.

Aspergillus-mediated allergic airway inflammation is triggered by dendritic cell recognition of a defined spore morphotype.

Background: Exposure to fungi, especially Aspergillus fumigatus, can elicit potent allergic inflammation that triggers and worsens asthmatic disease. Dendritic cells (DCs) initiate allergic inflammatory responses to allergic stimuli. However, it is unclear if Af spores during isotropic growth (early spore swelling) can activate DCs to initiate allergic responses or if germination is required.

A one health roadmap towards understanding and mitigating emerging Fungal Antimicrobial Resistance: fAMR.

The emergence of fungal antimicrobial resistance-fAMR-is having a growing impact on human and animal health, and food security. This roadmap charts inter-related actions that will enhance our ability to mitigate the risk of fAMR. As humanity's reliance on antifungal chemicals escalates, our understanding of their one-health consequences needs to scale accordingly if we are to protect our ability to manage the global spectrum of fungal disease sustainably.

Shining a light on the impact of antifungals on subcellular dynamics through fluorescence imaging.

Fluorescent proteins (FPs) are indispensable tools used for molecular imaging, single-cell dynamics, imaging in infection models, and more. However, next-generation FPs have yet to be characterized in . Here, we characterize 18 FPs in the pathogenic filamentous fungus spanning the visible light spectrum.

Discontinuation of Antidepressants and the Risk of Medication Resumption among Community-Dwelling Older Adults with Depression in the US.

Antidepressants are among the most prescribed drugs in the US, but the current treatment patterns and modalities among older adults are unclear. This study assessed the patterns of discontinuation of antidepressants and the risk of medication resumption among community-dwelling older adults with depression. Using Medicare Current Beneficiary Survey (MCBS) data from 2015-2019, we identified 1084 beneficiaries with depression who newly initiated serotonergic antidepressants.

The Transcription Factors AcuK and AcuM Influence Siderophore Biosynthesis of .

The mold employs two high-affinity uptake systems, reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA), for the acquisition of the essential trace element iron. SIA has previously been shown to be crucial for virulence in mammalian hosts. Here, we show that a lack of AcuK or AcuM, transcription factors required for the activation of gluconeogenesis, decreases the production of both extra- and intracellular siderophores in .

Analysis of Early Iron Sulfide, Carbonate, and Phosphate Mineral Analogues Produced by Flow-Driven Precipitation in a Microchannel.

Most of the chemical and physical interactions of interest to the astrobiology community are influenced by the mineralogy of the systems under consideration. Often, this mineralogy occurs in sediment or sediment-like aqueous microenvironments in which the early minerals differ dramatically from the mature version that results from a long diagenesis, which are tied to complex interactions of pH, redox state, concentration, and temperature. This interconnectedness is difficult to reproduce in a laboratory setting yet is essential to understanding how the physical and chemical demands of living systems alter and are altered by their geological context.

Development of a novel mycobiome diagnostic for fungal infection.

Background: Amplicon-based mycobiome analysis has the potential to identify all fungal species within a sample and hence could provide a valuable diagnostic assay for use in clinical mycology settings. In the last decade, the mycobiome has been increasingly characterised by targeting the internal transcribed spacer (ITS) regions. Although ITS targets give broad coverage and high sensitivity, they fail to provide accurate quantitation as the copy number of ITS regions in fungal genomes is highly variable even within species.

Burden of Chronic and Heavy Opioid Use Among Elderly Community Dwellers in the U.S.

Introduction: Opioid overprescribing may fuel the opioid epidemic and increase the risk of complications of opioid misuse. This study examined trends and determinants of chronic and heavy opioid use among elderly community dwellers in the U.S.

Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection.

Aspergillus fumigatus is a saprophytic fungus that can cause a variety of human diseases known as aspergillosis. Mycotoxin gliotoxin (GT) production is important for its virulence and must be tightly regulated to avoid excess production and toxicity to the fungus. GT self-protection by GliT oxidoreductase and GtmA methyltransferase activities is related to the subcellular localization of these enzymes and how GT can be sequestered from the cytoplasm to avoid increased cell damage.

Aspergillus fumigatus strains that evolve resistance to the agrochemical fungicide ipflufenoquin in vitro are also resistant to olorofim.

Widespread use of azole antifungals in agriculture has been linked to resistance in the pathogenic fungus Aspergillus fumigatus. We show that exposure of A. fumigatus to the agrochemical fungicide, ipflufenoquin, in vitro can select for strains that are resistant to olorofim, a first-in-class clinical antifungal with the same mechanism of action.

A phylogenetic approach to explore the conidial surface-associated proteome and its role in pathogenesis.

, an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores (conidia) for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface of , two closely related non-pathogenic species, and , and the cryptic pathogen . After identifying 62 proteins uniquely expressed on the conidial surface, we assessed null mutants for 42 genes encoding conidial proteins.

Functional analysis of the kinome reveals a DYRK kinase involved in septal plugging is a novel antifungal drug target.

More than 10 million people suffer from lung diseases caused by the pathogenic fungus . The azole class of antifungals represent first line therapeutics for most of these infections however resistance is rising. Identification of novel antifungal targets that, when inhibited, synergise with the azoles will aid the development of agents that can improve therapeutic outcomes and supress the emergence of resistance.

Vacuoles and peroxisomes are involved in gliotoxin production and self-protection.

is a saprophytic fungus that can cause a variety of human diseases known as aspergillosis. Mycotoxin gliotoxin (GT) production is important for its virulence and must be tightly regulated to avoid excess production and toxicity to the fungus. GT self-protection by GliT oxidoreductase and GtmA methyltransferase activities is related to the subcellular localization of these enzymes and how GT can be sequestered from the cytoplasm to avoid increased cell damage.

The CH transcription factor SltA is required for germination and hyphal development in .

Germination of inhaled conidia is a necessary sequitur for infection. Germination of conidia starts with the breaking of dormancy, which is initiated by an increase of the cellular perimeter in a process termed isotropic growth. This swelling phase is followed by polarized growth, resulting in the formation of a germ tube.

Disruption of the RNA interference machinery alters the conidial transcriptome.

The RNA interference (RNAi) pathway has evolved numerous functionalities in eukaryotes, with many on display in Kingdom Fungi. RNAi can regulate gene expression, facilitate drug resistance, or even be altogether lost to improve growth potential in some fungal pathogens. In the WHO fungal priority pathogen, , the RNAi system is known to be intact and functional.