Pan-omics-based characterization and prediction of highly multidrug-adapted strains from an outbreak fungal species complex.

Strains from the species complex (CGSC) have caused the Pacific Northwest cryptococcosis outbreak, the largest cluster of life-threatening fungal infections in otherwise healthy human hosts known to date. In this study, we utilized a pan-phenome-based method to assess the fitness outcomes of CGSC strains under 31 stress conditions, providing a comprehensive overview of 2,821 phenotype-strain associations within this pathogenic clade. Phenotypic clustering analysis revealed a strong correlation between distinct types of stress phenotypes in a subset of CGSC strains, suggesting that shared determinants coordinate their adaptations to various stresses.

Nitrate assimilation compensates for cell wall biosynthesis in the absence of phosphoglucose isomerase.

Phosphoglucose isomerase (PGI) links glycolysis, the pentose phosphate pathway (PPP), and the synthesis of cell wall precursors in fungi by facilitating the reversible conversion between glucose-6-phosphate (Glc6p) and fructose-6-phosphate (Fru6P). In a previous study, we established the essential role of PGI in cell wall biosynthesis in the opportunistic human fungal pathogen , highlighting its potential as a therapeutic target. In this study, we conducted transcriptomic analysis and discovered that the Δ mutant exhibited enhanced glycolysis, reduced PPP, and an upregulation of cell wall precursor biosynthesis pathways.

Understanding underlying physical mechanism reveals early warning indicators and key elements for adaptive infections disease networks.

The study of infectious diseases holds significant scientific and societal importance, yet current research on the mechanisms of disease emergence and prediction methods still face challenging issues. This research uses the landscape and flux theoretical framework to reveal the non-equilibrium dynamics of adaptive infectious diseases and uncover its underlying physical mechanism. This allows the quantification of dynamics, characterizing the system with two basins of attraction determined by gradient and rotational flux forces.

Self-Assembled Aza-Boron-Dipyrromethene-Based HS Prodrug for Synergistic Ferroptosis-Enabled Gas and Sonodynamic Tumor Therapies.

Glioblastoma multiforme (GBM) is the most aggressive and lethal subtype of gliomas of the central nervous system. The efficacy of sonodynamic therapy (SDT) against GBM is significantly reduced by the expression of apoptosis-inhibitory proteins in GBM cells. In this study, an intelligent nanoplatform (denoted as Aza-BD@PC NPs) based on the aza-boron-dipyrromethene dye and phenyl chlorothionocarbonate-modified DSPE-PEG molecules is developed for synergistic ferroptosis-enabled gas therapy (GT) and SDT of GBM.

Early warning indicators of war and peace through the landscapes and flux quantifications.

War and peace, spanning history, deeply affect society, economy, and individuals. Grasping their dynamics is vital to lessen harm and foster global peace. Yet, quantifying them remains hard.

Brain glucose induces tolerance of Cryptococcus neoformans to amphotericin B during meningitis.

Antibiotic tolerance is the ability of a susceptible population to survive high doses of cidal drugs and has been shown to compromise therapeutic outcomes in bacterial infections. In comparison, whether fungicide tolerance can be induced by host-derived factors during fungal diseases remains largely unknown. Here, through a systematic evaluation of metabolite-drug-fungal interactions in the leading fungal meningitis pathogen, Cryptococcus neoformans, we found that brain glucose induces fungal tolerance to amphotericin B (AmB) in mouse brain tissue and patient cerebrospinal fluid via the fungal glucose repression activator Mig1.

Fungicide-tolerant persister formation during cryptococcal pulmonary infection.

Bacterial persisters, a subpopulation of genetically susceptible cells that are normally dormant and tolerant to bactericides, have been studied extensively because of their clinical importance. In comparison, much less is known about the determinants underlying fungicide-tolerant fungal persister formation in vivo. Here, we report that during mouse lung infection, Cryptococcus neoformans forms persisters that are highly tolerant to amphotericin B (AmB), the standard of care for treating cryptococcosis.

Amino sugars influence Aspergillus fumigatus cell wall polysaccharide biosynthesis, and biofilm formation through interfering galactosaminogalactan deacetylation.

Aspergillus fumigatus is a ubiquitous fungal pathogen responsible for a significant number of deaths annually due to invasive aspergillosis infection. While the utilization of diverse carbon sources, including amino sugars, has been explored in other fungi, its impact on A. fumigatus remains uncharted territory.

Virulence profiling of isolates in China: insights from a multi-center study.

Our study indicates that the molecular typing of is unrelated to virulence. The integration of animal experiments and clinical prognosis demonstrated that pathogenicity did not exhibit a direct correlation with virulence phenotypes or molecular genotypes, emphasizing the intricate nature of virulence. In conclusion, our research holds the potential to provide valuable insights into understanding the microbiological attributes of in China.

A Pipeline for Constructing Reference Genomes for Large Cohort-Specific Metagenome Compression.

Metagenomic data compression is very important as metagenomic projects are facing the challenges of larger data volumes per sample and more samples nowadays. Reference-based compression is a promising method to obtain a high compression ratio. However, existing microbial reference genome databases are not suitable to be directly used as references for compression due to their large size and redundancy, and different metagenomic cohorts often have various microbial compositions.

Confronting antifungal resistance, tolerance, and persistence: Advances in drug target discovery and delivery systems.

Human pathogenic fungi pose a serious threat to human health and safety. Unfortunately, the limited number of antifungal options is exacerbated by the continuous emergence of drug-resistant variants, leading to frequent drug treatment failures. Recent studies have also highlighted the clinical importance of other modes of fungal survival of antifungal treatment, including drug tolerance and persistence, pointing to the complexity of the fungal response to antifungal drugs.

Reachable set estimation and stochastic sampled-data exponential synchronization of Markovian jump neural networks with time-varying delays.

In this paper, the stochastic sampled-data exponential synchronization problem for Markovian jump neural networks (MJNNs) with time-varying delays and the reachable set estimation (RSE) problem for MJNNs subjected to external disturbances are investigated. Firstly, assuming that two sampled-data periods satisfy Bernoulli distribution, and introducing two stochastic variables to represent the unknown input delay and the sampled-data period respectively, the mode-dependent two-sided loop-based Lyapunov functional (TSLBLF) is constructed, and the conditions for the mean square exponential stability of the error system are derived. Furthermore, a mode-dependent stochastic sampled-data controller is designed.

Cryptococcus neoformans, a global threat to human health.

Background: Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL, Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance.

Correction: Molecular epidemiology and microbiological characteristics of Cryptococcus gattii VGII isolates from China.

[This corrects the article DOI: 10.1371/journal.pntd.

Regulatory basis for reproductive flexibility in a meningitis-causing fungal pathogen.

Pathogenic fungi of the genus Cryptococcus can undergo two sexual cycles, involving either bisexual diploidization (after fusion of haploid cells of different mating type) or unisexual diploidization (by autodiploidization of a single cell). Here, we construct a gene-deletion library for 111 transcription factor genes in Cryptococcus deneoformans, and explore the roles of these regulatory networks in the two reproductive modes. We show that transcription factors crucial for bisexual syngamy induce the expression of known mating determinants as well as other conserved genes of unknown function.

Connectivity from ipsilateral and contralateral dorsolateral prefrontal cortex to the active primary motor cortex during approaching-avoiding behavior.

Automatic action tendency is reflected by a fast reaction to approach positive stimulus and to avoid negative stimulus (automatic behaviors), while a slow reaction to approach negative stimulus and avoid positive stimulus (controlled behaviors). The dorsolateral prefrontal cortex (DLPFC) is involved in the modulation of the automatic action tendency; however, it remains unclear whether DLPFC modulates the behavior through motor inhibition or excitation, as well as the exact timing of the modulation. We used paired-pulse, dual-site TMS protocols to investigate the connectivity between left/right DLPFC and the left primary motor cortex (M1) during the manikin task performed with the right hand.

Detecting Genetic Variation of Colonizing Genomes in Humans: A Precision Protocol.

Deciphering the genotypic diversity of within-individual pathogens and verifying the evolutionary model can help elucidate resistant genotypes, virulent subpopulations, and the mechanism of opportunistic pathogenicity. However, observed polymorphic mutations (PMs) are rare and difficult to be detected in the "dominant-lineage" model of bacterial infection due to the low frequency. The four pooled group B (GBS) samples were collected from the genital tracts of healthy pregnant women, and the pooled samples and the isogenic controls were genomically sequenced.

Genome-wide identification and expression analysis of the ftsH protein family and its response to abiotic stress in Nicotiana tabacum L.

Background: The filamentous temperature-sensitive H protease (ftsH) gene family plays an important role in plant growth and development. FtsH proteins belong to the AAA protease family. Studies have shown that it is a key gene for plant chloroplast development and photosynthesis regulation.

Functional Characterization of the GlcNAc Catabolic Pathway in Cryptococcus deneoformans.

The amino sugar -acetyl-d-glucosamine (GlcNAc) is the key constituent of cell wall components and plays an important role in pathogenesis in a wide range of fungi. However, catabolism of GlcNAc has not been studied in basidiomycete fungi. In this study, we identified and characterized a gene cluster essential for GlcNAc utilization in Cryptococcus deneoformans, an environmental human fungal pathogen.

Plant sterol ester of α-linolenic acid improved non-alcoholic fatty liver disease by attenuating endoplasmic reticulum stress-triggered apoptosis via activation of the AMPK.

Apoptosis is a feature of progressions steatosis to nonalcoholic steatohepatitis (NASH) and can be explained by endoplasmic reticulum stress (ERS). The present study aimed to investigate the protective effects of plant sterol ester of α-linolenic acid (PS-ALA) on ERS-triggered apoptosis in high fat diet-fed mice and oleic acid-induced hepatocytes, and further explore the underlying mechanisms. Our results showed that PS-ALA improved Non-alcoholic fatty liver disease (NAFLD) in both in vivo and in vitro models.