Transcription activator-like effectors from endosymbiotic bacteria control the reproduction of their fungal host.

Interactions between fungi and bacteria are critically important in ecology, medicine, and biotechnology. In this study, we shed light on factors that promote the persistence of a toxin-producing, phytopathogenic symbiosis that causes severe crop losses in Asia. We present an unprecedented case where bacterially produced transcription activator-like (TAL) effectors are key to maintaining a stable endosymbiosis.

Streptomyces alleviate abiotic stress in plant by producing pteridic acids.

Soil microbiota can confer fitness advantages to plants and increase crop resilience to drought and other abiotic stressors. However, there is little evidence on the mechanisms correlating a microbial trait with plant abiotic stress tolerance. Here, we report that Streptomyces effectively alleviate drought and salinity stress by producing spiroketal polyketide pteridic acid H (1) and its isomer F (2), both of which promote root growth in Arabidopsis at a concentration of 1.

COVID-19 in Patients with Active Cancer: Higher Inflammatory Activity Predicts Poor Outcome.

Introduction: Active malignancies have been identified as an independent risk factor for severity and mortality in COVID-19. However, direct comparisons between SARS-CoV-2-infected patients with active (acP) and non-active cancers (n-acP) remain scarce.

Patients And Methods: We retrospectively analyzed a cohort of cancer patients with PCR-confirmed SARS-CoV-2 infection, enrolled from March 16, 2020, to July 31, 2021.

Distinct transcriptional responses to fludioxonil in Aspergillus fumigatus and its ΔtcsC and Δskn7 mutants reveal a crucial role for Skn7 in the cell wall reorganizations triggered by this antifungal.

Background: Aspergillus fumigatus is a major fungal pathogen that causes severe problems due to its increasing resistance to many therapeutic agents. Fludioxonil is a compound that triggers a lethal activation of the fungal-specific High Osmolarity Glycerol pathway. Its pronounced antifungal activity against A.

Quantitative analysis of peroxisome tracks using a Hidden Markov Model.

Diffusion and mobility are essential for cellular functions, as molecules are usually distributed throughout the cell and have to meet to interact and perform their function. This also involves the cytosolic migration of cellular organelles. However, observing such diffusion and interaction dynamics is challenging due to the high spatial and temporal resolution required and the accurate analysis of the diffusional tracks.

Glass Microneedles: A Case Study for Regulatory Approval Using a Quality by Design Approach.

In this paper, a roadmap is provided for the regulatory approval of one of the exciting and dynamic drug delivery fields, microneedles, by using a Quality by Design approach to pharmaceutical product development. In this regard, a quality target product profile (QTPP) and the critical quality attributes (CQA) of microneedles are identified. A case study of the recently patented method of fabricating glass microneedles entirely from a therapeutic agent, thus eliminating the requirement for additional excipients is discussed.

Laboratory-Based Correlative Soft X-ray and Fluorescence Microscopy in an Integrated Setup.

Correlative microscopy is a powerful technique that combines the advantages of multiple imaging modalities to achieve a comprehensive understanding of investigated samples. For example, fluorescence microscopy provides unique functional contrast by imaging only specifically labeled components, especially in biological samples. However, the achievable structural information on the sample in its full complexity is limited.

Novel Calcium-Binding Motif Stabilizes and Increases the Activity of Ecto-NADase.

Nicotinamide adenine dinucleotide (NAD) is an essential molecule in all kingdoms of life, mediating energy metabolism and cellular signaling. Recently, a new class of highly active fungal surface NADases was discovered. The enzyme from the opportunistic human pathogen was thoroughly characterized.

Contribution of radixin and ezrin to the maintenance of hepatocytes' excretory function in health and disease.

Background & Aims: Excretory liver failure is frequently associated with poor prognosis in critically ill patients. It is characterized by the loss of canalicular membrane export pumps at the hepatocyte membrane. The membrane export pump Multidrug resistant-associated protein (MRP) 2 is pivotal in hepatocytes for brushed membrane morphology and transport of various metabolites.

Bacterial Isothiocyanate Biosynthesis by Rhodanese-Catalyzed Sulfur Transfer onto Isonitriles.

Natural products bearing isothiocyanate (ITC) groups are an important group of specialized metabolites that play various roles in health, nutrition, and ecology. Whereas ITC biosynthesis via glucosinolates in plants has been studied in detail, there is a gap in understanding the bacterial route to specialized metabolites with such reactive heterocumulene groups, as in the antifungal sinapigladioside from Burkholderia gladioli. Here we propose an alternative ITC pathway by enzymatic sulfur transfer onto isonitriles catalyzed by rhodanese-like enzymes (thiosulfate:cyanide sulfurtransferases).

Nonribosomal peptides protect 4A2e from amoebal and nematodal predation.

The rhizosphere is a highly competitive environment forcing bacteria to evolve strategies to oppose their enemies. The production of toxic secondary metabolites allows bacteria to counteract predators. In this study, we describe the anti-predator armamentarium of the soil-derived bacterium 4A2e.

Public health risk communication through the lens of a quarantined community: Insights from a coronavirus hotspot in Germany.

Background: Quarantine is one of the most effective interventions to contain an infectious disease outbreak, yet it is one of the most disruptive. We investigated the quarantine of an entire village to better understand risk communication requirements for groups.

Methods: We conducted a cross-sectional, mixed-methods survey study on a single cohort of adult residents in Neustadt am Rennsteig, Germany, six weeks after the removal of a 14-day mandatory community quarantine.

Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis.

The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer's disease (AD), but the molecular basis of brain anti-Candida immunity remains unknown. We show that C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted aspartic proteinases (Saps) and candidalysin.

Analysing Megasynthetase Mutants at High Throughput Using Droplet Microfluidics.

Nonribosomal peptide synthetases (NRPSs) are giant enzymatic assembly lines that deliver many pharmaceutically valuable natural products, including antibiotics. As the search for new antibiotics motivates attempts to redesign nonribosomal metabolic pathways, more robust and rapid sorting and screening platforms are needed. Here, we establish a microfluidic platform that reliably detects production of the model nonribosomal peptide gramicidin S.

Candida albicans induces neutrophil extracellular traps and leucotoxic hypercitrullination via candidalysin.

The peptide toxin candidalysin, secreted by Candida albicans hyphae, promotes stimulation of neutrophil extracellular traps (NETs). However, candidalysin alone triggers a distinct mechanism for NET-like structures (NLS), which are more compact and less fibrous than canonical NETs. Candidalysin activates NADPH oxidase and calcium influx, with both processes contributing to morphological changes in neutrophils resulting in NLS formation.

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.

Exploring Longitudinal Gut Microbiome towards Metabolic Functional Changes Associated in Atopic Dermatitis in Early Childhood.

Atopic dermatitis (AD) is a prevalent inflammatory skin disease that has been associated with changes in gut microbial composition in early life. However, there are limited longitudinal studies examining the gut microbiome in AD. This study aimed to explore taxonomy and metabolic functions across longitudinal gut microbiomes associated with AD in early childhood from 9 to 30 months of age using integrative data analysis within the Thai population.

Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic T1 cell responses in Crohn's disease.

Aberrant CD4 T cell reactivity against intestinal microorganisms is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microorganism-specific, pathogenic T cell phenotypes remain largely unknown. In the present study, we identified common gut commensal and food-derived yeasts, as direct activators of altered CD4 T cell reactions in patients with Crohn's disease (CD).

Novel Biocatalysts from Specialized Metabolism.

Enzymes are increasingly recognized as valuable (bio)catalysts that complement existing synthetic methods. However, the range of biotransformations used in the laboratory is limited. Here we give an overview on the biosynthesis-inspired discovery of novel biocatalysts that address various synthetic challenges.

Isolation of sulfonosphingolipids from the rosette-inducing bacterium and evaluation of their rosette-inducing activity.

The choanoflagellate transitions from unicellular to multicellular forms in the presence of bacterial signaling molecules, such as sulfonosphingolipids (RIFs). We set out to characterize the abundance of RIF-like molecules within five different Bacteroidetes strains belonging to different genera. While four strains exhibited similar sulfonosphingolipid profiles with sulfobacin A as the dominant feature, the composition in differed distinctively.

Comparative genomic analysis of Fusobacterium nucleatum reveals high intra-species diversity and cgmlst marker construction.

Background: Fusobacterium nucleatum is a one of the most important anaerobic opportunistic pathogens in the oral and intestinal tracts of human and animals. It can cause various diseases such as infections, Lemierre's syndrome, oral cancer and colorectal cancer. The comparative genomic studies on the population genome level, have not been reported.

Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations.

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic dysfunction for which effective interventions are lacking. To investigate the effects of resistant starch (RS) as a microbiota-directed dietary supplement for NAFLD treatment, we coupled a 4-month randomized placebo-controlled clinical trial in individuals with NAFLD (ChiCTR-IOR-15007519) with metagenomics and metabolomics analysis. Relative to the control (n = 97), the RS intervention (n = 99) resulted in a 9.

Non-canonical two-step biosynthesis of anti-oomycete indole alkaloids in Kickxellales.

Background: Fungi are prolific producers of bioactive small molecules of pharmaceutical or agricultural interest. The secondary metabolism of higher fungi (Dikarya) has been well-investigated which led to > 39,000 described compounds. However, natural product researchers scarcely drew attention to early-diverging fungi (Mucoro- and Zoopagomycota) as they are considered to rarely produce secondary metabolites.