Type I interferon (IFN-I) responses are tightly regulated to balance antiviral defense with cellular homeostasis. In humans, interferon-stimulated gene 15 (ISG15) functions as a critical negative regulator of IFN-I signaling by stabilizing the IFN negative regulator USP18, yet the functional consequences of ISG15 deficiency remain elusive. Here, we show that the loss of ISG15 exaggerates […]
Genome-wide mapping of gene essentiality in Pseudomonas chlororaphis ATCC 9446 using transposon mutagenesis.
Pseudomonas chlororaphis ATCC 9446 is a non-pathogenic rhizobacterium with biotechnological relevance as a biocontrol agent and a promising chassis for synthetic biology. Understanding which genes are strictly required for survival is fundamental to both bacterial physiology and chassis engineering. Here, we generate a genome-wide map of genetic essentiality for P. chlororaphis using high-density Random Barcoded […]
Improving the production and virulence of entomopathogenic fungi for biological control using insect-derived in vitro culture medium
The environment in which a fungus grows can directly influence their development, transmission, and pathogenic potential. This environment encompasses factors like nutrient availability, biotic and abiotic stressors, as well as host-derived chemical cues. In fungal pathogens, where conidia act as the infectious agents, the environment impacts the quantity and quality of these spores, thereby affecting […]
Mitochondrial DNA Variation in the D-LOOP and ND Loci identified in the Kenyan Population: Potential Implications for precision Oncology
Background: Precision oncology is predominantly focused on nuclear genomic alterations, while mitochondrial DNA (mtDNA) variation remains largely excluded from routine pharmacogenomic testing. However, mitochondria regulate oxidative phosphorylation (OXPHOS), reactive oxygen species (ROS) production, apoptosis, and metabolic reprogramming pathways central to chemotherapy response. Methods: 468 Complete mitochondrial genomes from Kenyan individuals representing diverse ethnolinguistic groups were […]
Stage-specific metabolic rewiring coordinates nucleotide supply and demand during spermatogenesis
Male meiotic prophase I features a major transition from leptotene/zygotene (LZ) to pachytene/diplotene (PD) spermatocytes, accompanied by rapid growth and extensive transcriptional remodeling. Using stage-resolved purification of spermatogenic populations integrated with Seahorse respirometry, proteomics/metabolomics, and stable-isotope tracing, we define metabolic programs across this transition. LZ spermatocytes show little oxidative response to glucose or lactate and […]
Identification of targetable epitope surfaces from the high resolution structure of the superantigen Staphylococcal Enterotoxin L
Emetic exotoxins secreted by Staphylococcus species (Staphylococcal enterotoxins, SEs) are a major cause of food poisoning cases worldwide and many are additionally classified as superantigens – able to potently activate T cells in an antigen independent manner. Fewer than half of the gene products of the known SE genes have been extensively characterized. The gene […]
Structural Basis of Serine Protease Inhibition by Antibodies from Biased Fab Phage-Display Libraries
Biased Fab phage-display libraries were designed to determine whether inhibitory CDR H3 motifs from potent anti-matriptase antibodies could be transferred to target homologous serine proteases. Using reverse-binding and substrate-like H3 motifs from parental clones A11 and E2 as templates, six synthetic libraries with 1010 diversity were constructed. Selection against matriptase identified sixteen inhibitors with sub-100~nM […]
Blautia wexlerae Transforms Dietary Fatty Acids to Activate Enteroendocrine Signaling and Improve Metabolic Health in Mice and Humans
Metabolites produced by the human gut microbiome influence host metabolic health, but how this occurs remains incompletely defined. Here, we report that a common human gut commensal, Blautia wexlerae, converts dietary fats into bioactive metabolites that induce gut hormone production to affect glucose metabolism and suppress appetite. We found that colonization with Blautia wexlerae correlated […]
Sample-derived cDNA guides broad host RNA depletion for in vivo pathogen transcriptomics
RNA sequencing has transformed our understanding of host-microbe interactions, yet in vivo profiling of bacterial pathogenesis remains fundamentally limited by the dominance of host RNA. Traditional rRNA depletion strategies fail to eliminate the vast background of host messenger and non-coding RNAs, resulting in poor pathogen coverage and necessitating cost-prohibitive deep sequencing. Here, we present a […]
Metabarcoding reveals that bacterial and fungal microbiomes are perturbed by micropollutants in a fjord system (Hakefjorden and Askerofjorden) at the Swedish west coast
Fjord systems are susceptible to anthropogenic pressures, including discharges from wastewater treatment plants (WWTPs), which introduce micropollutants into coastal waters. We investigated the impact of micropollutants on bacteria and fungi within a fjord system adjacent to a significant petrochemical industry hub on the Swedish west coast. We characterised microbial assemblages along a land-to-sea transect, encompassing […]
DNA methylation variability defines a fundamental dimension of tumor epigenomes linked to genomic instability, tumor aggressiveness, and clinical outcomes
Background Tumors exhibit substantial cellular and molecular diversity driven by genetic and epigenetic mechanisms. Large scale profiling efforts have established aberrant DNA methylation as a universal hallmark of cancer. Beyond changes in mean methylation levels, tumor tissues exhibit elevated DNA methylation variability at specific genomic regions within and across tumors. This constitutes a fundamental dimension […]
Cross-family and phage-specific gene requirements for Klebsiella infection revealed by scalable RB-TnSeq genetic screens
Bacteriophages (phages) are being cataloged at unprecedented rates and are recognized as key players in nutrient and energy cycling across ecosystems. Yet, the biological determinants of phage-host specificity and infection success remain poorly understood. Here, we used a randomly barcoded, genome-wide, loss-of-function transposon mutant library (RB-TnSeq) of Klebsiella sp. M5al, a plant-associated, nitrogen-fixing rhizobacterium, to […]