Project description:The mammalian immune system is constantly challenged by signals from both pathogenic and non-pathogenic microbes. Many of these non-pathogenic microbes have pathogenic potential if the immune system is compromised. The importance of type I interferons (IFNs) in orchestrating innate immune responses to pathogenic microbes has become clear in recent years. However, the control of opportunistic pathogens – and especially intracellular bacteria – by type I IFNs remains less appreciated. In this study, we use the opportunistic, Gram-negative bacterial pathogen Burkholderia cenocepacia (Bc) to show that type I IFNs are capable of limiting bacterial replication in macrophages, preventing illness in immunocompetent mice. Sustained type I IFN signaling through cytosolic receptors allows for increased expression of autophagy and linear ubiquitination mediators, which slows bacterial replication. Transcriptomic analyses and in vivo studies also show that LPS stimulation does not replicate the conditions of intracellular Gram-negative bacterial infection as it pertains to type I IFN stimulation or signaling. This study highlights the importance of type I IFNs in protection against opportunistic pathogens through innate immunity, without the need for damaging inflammatory responses.
Project description:Leaves are colonised by a complex mix of microbes, termed the leaf microbiota. Even though the leaf microbiota is increasingly recognised as an integral part of plant life and health, our understanding of its interactions with the plant host is still limited. Here, mature, axenically grown Arabidopsis thaliana plants were spray-inoculated with diverse leaf-colonising bacteria. Whole transcriptome sequencing revealed that four days after inoculation, leaf transcriptional changes to colonisation by non-pathogenic and pathogenic bacteria differed in strength but not in the type of response.
Project description:Mutational inactivation of ?-thalassaemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of adult and pediatric malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures at GC-rich regions of the genome, altering chromatin accessibility and enhancing DNA damage. Building on earlier work, we sought to assess the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in preclinical models of ATRX-deficient glioma. To investigate the effect of G4 stabilization on histone variant H3.3 deposition on the genome, we treated patient-derived glioma stem cells (GSCs) with G4 stabilizer CX-5461 and performed cleavage under targets and tagmentation (CUT&Tag) for H3.3. Our analyses show that G4 stabilizer CX-541 disrupts H3.3 deposition in ATRX-deficient GSCs and likely enhances replication stress and DNA damage.
Project description:The gastrointestinal tract is a major site of early HIV-1 replication and death of CD4+ T cells. As HIV-1 replicates in the gut, the protective epithelial barrier gets disrupted, leading to the entry of bacteria into the underlying tissue and the bloodstream, leading to inflammation and clinical complications even in HIV-1-infected patients taking antiviral drugs. Counteracting these pathogenic processes may require in-depth understanding of the molecular pathways that HIV-1 and microbes utilize to infect, functionally alter and/or kill CD4+ T cells. However, to date, the nature of the genes altered by relevant HIV-1 strains and bacteria in intestinal CD4+ T cells remains unclear. Here, we obtained the first gene expression profiles of transmitted/founder (TF) HIV-1 (CH40-T2A-eGFP) infected gut CD4+ T cells infected with HIV-1 in the context of microbes found in the GI tract of HIV-1 infected patients. Our findings reveal common and distinct signaling pathways altered by HIV-1 depending on the presence of microbes that may shed light on infection, inflammation and CD4+ T cell depletion in HIV-1 infected individuals. In-depth understanding of these molecular programs may inform potential ways to counteract pathogenic outcomes initiated and/or sustained by HIV-1 infection in the GI tract.
Project description:Leaves are colonised by a complex mix of microbes, termed the leaf microbiota. Even though the leaf microbiota is increasingly recognised as an integral part of plant life and health, our understanding of its interactions with the plant host is still limited. Here, mature, axenically grown Arabidopsis thaliana plants were spray-inoculated with diverse leaf-colonising bacteria. Whole transcriptome sequencing revealed that four days after inoculation, leaf transcriptional changes to colonisation by non-pathogenic and pathogenic bacteria differed in strength but not in the type of response. Inoculation of plants with different densities of the non-pathogenic bacterium Williamsia sp. Leaf354 showed that high bacterial titers caused disease phenotypes and led to severe transcriptional reprogramming with a strong focus on plant defence. This SuperSeries is composed of the SubSeries listed below.
Project description:Plants establish mutualistic association with beneficial microbes while deploy the immune system to defend against pathogens. Little is known about the interplay between mutualism and immunity and about the mediator molecules. Here we show that plants respond differently to a bacterial volatile compound through integral modulation of the immune system and the phosphate starvation response (PSR) system, resulting in either mutualism or immunity. We found that the same exposure of a recognized plant growth-promoting rhizobacterium unexpectedly causes either beneficial or deleterious effects to plants. The beneficial-to-deleterious transition is dependent on plant nutrition of phosphorus (P) and is mediated by diacetyl (DA), a bacterial volatile compound. In P-sufficient plants, DA partially suppresses plant production of reactive oxygen species (ROS) and enhances symbiont colonization without compromising disease resistance. In P-deficient plants, DA elevates phytohormone-mediated immunity and consequently causes plant hypersensitivity to P deficiency. Therefore, DA affects the types of relation between plants and certain rhizobacteria in a way that depends on plant PSR system and phytohormone-mediated immunity.
Project description:Leaves are colonised by a complex mix of microbes, termed the leaf microbiota. Even though the leaf microbiota is increasingly recognised as an integral part of plant life and health, our understanding of its interactions with the plant host is still limited. Here, mature, axenically grown Arabidopsis thaliana plants were spray-inoculated with different densities of the non-pathogenic bacterium Williamsia sp. Leaf354. High bacterial titers caused disease phenotypes and led to severe transcriptional reprogramming with a strong focus on plant defence.
Project description:During growth in their ecological niche fungi encounter many (micro)organisms that compete for nutrients and /or have antagonistic activity. However, little is known about responses of fungi upon exposure to other microbes. In this project we want to gain insight in induced responses of C. cinerea towards bacteria through comparison of the transcriptome of vegetative C. cinerea mycelium either grown alone or exposed to the bacterial species Escherichia coli or Bacillus subtilis
Project description:Cannabis sativa L., which has been reclassified as an agronomic crop, has experienced an increase in cultivation. Its interactions with a variety of environmental stressors have been extensively studied. However, the mechanisms of recovery through fungal associations remain underexplored. Trichoderma hamatum, known for its role as a biological agent, enhances plant growth and provides antagonistic defense against pathogenic microbes. This meta-dataset aims to investigate whether Th can enhance drought resistance in a Cannabis plants.