Biology subjects

Louet, C.

Publications and source records attributed to Louet, C..

5 recordsLinked to original sources

bioRxiv2022

Pyruvate supports RET-dependent mitochondrial ROS production necessary to control Mycobacterium avium infection in human primary macrophages

Macrophages deploy a variety of antimicrobial programs to contain mycobacterial infection. Upon activation, they undergo extensive metabolic reprogramming to meet an increase in energy demand, but also to support immune effector functions such as secretion of cytokines and antimicrobial activities. Here, we report that mitochondrial import of pyruvate is linked to production of mitochondrial ROS and control of Mycobacterium avium infection in human primary macrophages. Using chemical inhibition, targeted mass spectrometry and single cell image analysis, we show that macrophages infected with M. avium switched to aerobic glycolysis without any major imbalances in the tricarboxylic acid cycle or changes in the energy charge. Instead, we found that pyruvate import contributed to hyperpolarization of mitochondria in infected cells and increased production of mitochondrial reactive oxygen species by the complex I via reverse electron transport, which reduced the macrophage burden of M. avium. While mycobacterial infections are extremely difficult to treat and notoriously resistant to antibiotics, this work stresses out that compounds specifically inducing mitochondrial reactive oxygen species could present themself as valuable adjunct treatments.

immunology↗

bioRxiv2021

Expert annotation and life-cycle transcriptomics of transcription factors in rust fungi (Pucciniales) highlight the role of cold shock proteins in dormancy exit

Fungi of the order Pucciniales are obligate plant biotrophs causing rust diseases. They exhibit a complex life cycle with the production of up to five spore types, infection of two unrelated hosts and an overwintering stage. Transcription factors (TFs) are key regulators of gene expression in eukaryote cells. In order to better understand genetic programs expressed during major transitions of the rust life cycle, we surveyed the complement of TFs in fungal genomes with an emphasis on Pucciniales. We found that despite their large gene numbers, rust genomes have a reduced repertoire of TFs compared to other fungi. The proportions of C2H2 and Zinc cluster - two of the most represented TF families in fungi-indicate differences in their evolutionary relationships in Pucciniales and other fungal taxa. The cold shock protein (CSP) family showed a striking expansion in Pucciniomycotina with specific duplications in the order Pucciniales. The survey of expression profiles collected by transcriptomics along the life cycle of the poplar rust fungus revealed TF genes related to major biological transitions, e.g. response to environmental cues and host infection. Particularly, poplar rust CSPs were strongly expressed in basidia produced after the overwintering stage suggesting a possible role in dormancy exit. Expression during transition from dormant telia to basidia confirmed the specific expression of the three poplar rust CSP genes. Their heterologous expression in yeast improved cell growth after cold stress exposure, strengthening their implication in dormancy exit. This study addresses for the first time TF involved in developmental transition in the rust life cycle opening perspectives to further explore molecular regulation in the biology of the Pucciniales.

microbiology↗

bioRxiv2021

A comprehensive collection of transcriptome data to support life cycle analysis of the poplar rust fungus Melampsora larici-populina

Melampsora larici-populina is an obligate biotrophic plant pathogen responsible for the poplar rust disease. This fungus belongs to the taxonomical order Pucciniales and exhibits a complex heteroecious and macrocyclic life cycle, i.e. it has the capacity to infect two unrelated host plants, larch and poplar, and to form five distinct spore types through the year. The M. larici-populina genome has been sequenced and annotated in 2011 and since, different transcriptomic analyses were conducted at different stages with oligoarrays and later on with RNA-Seq covering most of its life cycle. Here, we collected published transcriptome data for the poplar rust fungus, transposed them for the version 2 of the genome now available at the Joint Genome Institute Mycocosm website and performed normalization of different oligoarray datasets on one hand, and of RNA-Seq on the other hand. We report a comprehensive normalized dataset for this fungus, made available for the community, which allows life cycle transcriptomics analysis.

microbiology↗

bioRxiv2021

Genomic signatures of a major adaptive event in the pathogenic fungus Melampsora larici-populina

BackgroundThe recent availability of genome-wide sequencing techniques has allowed systematic screening for molecular signatures of adaptation, including in non-model organisms. Host-pathogen interactions constitute good models due to the strong selective pressures that they entail. We focused on an adaptive event which affected the poplar rust fungus Melampsora larici-populina when it overcame a resistance gene borne by its host, cultivated poplar. Based on 76 virulent and avirulent isolates framing narrowly the estimated date of the adaptive event, we examined the molecular signatures of selection. ResultsUsing an array of genome scan methods, we detected a single locus exhibiting a consistent pattern suggestive of a selective sweep in virulent individuals (excess of differentiation between virulent and avirulent samples, linkage disequilibrium, genotype-phenotype statistical association and long-range haplotypes). Our study pinpoints a single gene and further a single amino acid replacement which may have allowed the adaptive event. Although the selective sweep occurred only four years earlier, it does not seem to have affected genome diversity further than the immediate vicinity of the causal locus. ConclusionsOur results suggest that M. larici-populina under-went a soft selective sweep and possibly a prominent effect of outbreeding and recombination, which we speculate have increased the efficiency of selection.

evolutionary biology↗

bioRxiv2021

Tapping into the aging brain: In vivo microdialysis reveals mirroring pathology between preclinical models and patients with Alzheimer's disease

Preclinical models of Alzheimers disease (AD) can provide valuable insights into the onset and progression of the disease, such as changes in concentrations of amyloid-{beta} (A{beta}) and tau in cerebrospinal fluid (CSF). However, such models are currently underutilized due to limited advancement in techniques that allow for longitudinal monitoring of CSF akin to methods employed in AD patients. An elegant way to understand the biochemical environment in the diseased brain is intracerebral microdialysis, a method that has until now been limited to short-term observations, or snapshots, of the brain microenvironment. Our novel push-pull microdialysis method in AD mice permits in vivo longitudinal monitoring of dynamic changes of A{beta} and tau in CSF and allows for better translational understanding of CSF biomarkers. Specifically, we demonstrate that CSF concentrations of A{beta} and tau along disease progression in transgenic mice mirror what is observed in patients, with a decrease in CSF A{beta} observed when plaques are deposited, and an increase in CSF tau once tau pathology is present in the brain. We found that a high molecular weight cut-off membrane allowed for simultaneous sampling of A{beta} and tau, comparable to lumbar puncture CSF collection in patients. We furthermore provide specific recommendations for optimal application of our novel microdialysis method, such as achieving optimal recovery of analytes, which depends heavily on the flow rate of perfusion, probe properties and perfusate composition. Our approach can further advance AD research by following evolving neuropathology along the disease cascade via consecutive sampling from the same animal, and can additionally be used to administer pharmaceutical compounds and assess their efficacy in treating AD.

neuroscience↗