Biology subjects

Michaux, J.

Publications and source records attributed to Michaux, J..

13 recordsLinked to original sources

bioRxiv2026

Exploring dog-owner microbiota and bacterial pathogens in Southeast Asia

Domestic dogs may influence human microbiota and act as reservoirs or sentinels for zoonotic bacteria, yet little is known about these dynamics in Southeast Asia. Using full-length 16S rRNA gene sequencing from rectal swabs, we analyzed microbiota from dog-owner pairs from four villages of rural Thailand (Nan province) to assess microbial diversity, shared taxa, and zoonotic potential. Dogs exhibited higher microbial and putative pathogen diversity than humans, particularly during the rainy season. While dog-owner pairs shared more bacteria than unrelated individuals, overall overlap remained limited - likely driven by their dogs free-roaming lifestyles and broader environmental exposures. However, co-occurrence of putative zoonotic pathogens such as Shigella spp. and Klebsiella pneumoniae suggests dogs could serve as useful indicators for specific public health risks, with further targeted pathogen screening needed to validate these results. Our findings highlight the value of integrating dogs into zoonotic surveillance programs, particularly in regions with free-ranging dog populations and close human-animal contact.

microbiology↗

bioRxiv2026

Sarbecovirus-associated gut microbiome instability in a natural bat reservoir

Sarbecoviruses, a subgenus of Betacoronavirus, display both respiratory and gastrointestinal tropism, suggesting potential interactions with host gut microbial communities. However, ecological signatures of infection in wild bats remain poorly understood. We investigated associations between Sarbecovirus infection status, gut microbiome structure, and diet composition in Rhinolophus shameli roosting in northeastern Cambodia. Fecal samples collected across dry and wet seasons (2023-2024) were subject to full-length 16S rRNA gene sequencing and arthropod DNA metabarcoding. Sarbecovirus-positive bats exhibited stable alpha diversity but consistent shifts in gut community composition and increased interindividual variability consistent with the Anna Karenina Principle, suggesting infection-associated destabilization of community assembly rather than diversity erosion. Infection status was associated with enrichment of Shigella and Escherichia species, taxa linked to inflammatory or epithelial stress states in bats. In contrast, dietary composition showed no strong global structuring by infection status and weak coupling with bacterial community structure, suggesting that trophic ecology is unlikely to be the main driver of the infection-associated microbiome signal. Although causal directionality cannot be inferred, our results reveal measurable and consistent microbiome restructuring associated with Sarbecovirus detection in a natural reservoir host and highlight the potential of microbiome profiling for monitoring wildlife disease processes.

ecology↗

bioRxiv2024

TCR-engineered T-cells directed against Ropporin-1 constitute a safe and effective treatment for triple-negative breast cancer in near-clinical models

Triple-negative breast cancer (TNBC) shows an urgent need for new therapies. We discovered Ropporin-1 (ROPN1) as a target to treat TNBC with T-cells. ROPN1 showed high and homogenous expression in 90% of primary and metastatic TNBC but not in healthy tissues. HLA-A2-binding peptides were detected via immunopeptidomics and predictions and used to retrieve T-cell receptors (TCRs) from naive repertoires. Following gene introduction into T-cells and stringent selection, we retrieved a highly specific TCR directed against the epitope FLYTYIAKV that did not recognize non-cognate epitopes from alternative source proteins. Notably, this TCR mediated killing of three-dimensional tumoroids in vitro and tumor cells in vivo and outperformed standard-of-care drugs. Finally, the T-cell product expressing this TCR and manufactured using a clinical protocol fulfilled standard safety and efficacy assays. Collectively, we have identified and preclinically validated ROPN1 as a target and anti-ROPN1 TCR T-cells as a treatment for the vast majority of TNBC patients.

immunology↗

bioRxiv2023

Continent-wide genomic analysis of the African buffalo (Syncerus caffer).

The African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest quality de novo genome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided surprisingly little support for the currently described four subspecies, but indicated three main lineages, in Western/Central, Eastern and Southern Africa, respectively. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.

genomics↗

bioRxiv2023

KRAB zinc finger proteins ZNF587/ZNF417 protect lymphoma cells from replicative stress-induced inflammation

Heterochromatin loss and genetic instability enhance cancer progression by favoring clonal diversity, yet uncontrolled replicative stress can lead to mitotic catastrophe and inflammatory responses promoting immune rejection. KRAB-containing zinc finger proteins (KZFPs) are epigenetic modulators, which for many control heterochromatin at transposable element (TE)-embedded regulatory sequences. We identified a cluster of 18 KZFPs associated with poor prognosis in diffuse large B cell lymphoma (DLBCL). We found their upregulation to correlate with increased copy number alterations and suppression of immune responses in tumor samples. Upon depleting two that target evolutionarily recent TEs, the primate-specific ZNF587 and ZNF417 paralogs, the proliferation of DLBCL cell lines was drastically impaired and replicative stress abruptly induced with marked alterations of the chromatin landscape and multiplication of DNA replication origins. Furthermore, ZNF587/417 knockdown upregulated interferon/inflammatory-related genes through activation of the cGAS-STING DNA sensing pathway, augmented the susceptibility of tumor cells to macrophage-mediated phagocytosis, and modified their immunogenicity through an increased surface expression of HLA-I and reshuffling of their immunopeptidome. ZNF587 and ZNF417 are thus pro-oncogenic factors allowing for higher degrees of genetic instability through attenuation of replicative stress and secondary inflammation, an influence that likely facilitates the clonal expansion, diversification, and immune evasion of cancer cells.

cancer biology↗

bioRxiv2022

Machine learning predictions of MHC-II specificities reveal alternative binding mode of class II epitopes

CD4+ T cells orchestrate the adaptive immune response against pathogens and cancer by recognizing epitopes presented on MHC-II molecules. The high polymorphism of MHC-II genes represents an important hurdle towards accurate prediction and identification of CD4+ T-cell epitopes in different individuals and different species. Here we collected and curated a dataset of 627,013 unique MHC-II ligands identified by mass spectrometry. This enabled us to precisely determine the binding motifs of 88 MHC-II alleles across human, mouse, cattle and chicken. Analysis of these binding specificities combined with X-ray crystallography refined our understanding of the molecular determinants of MHC-II motifs and revealed a widespread reverse binding mode in MHC-II ligands. We then developed a machine learning framework to accurately predict binding specificities and ligands of any MHC-II allele. This tool improves and expands predictions of CD4+ T-cell epitopes, and enabled us to discover and characterize several viral and bacterial epitopes following the aforementioned reverse binding mode.

immunology↗

bioRxiv2021

Extensive genome introgression between domestic ferret and European polecat during population recovery in Great Britain.

The European polecat (Mustela putorius) is a mammalian predator which occurs across much of Europe east to the Ural Mountains. In Great Britain, following years of persecution the European polecat has recently undergone a population increase due to legal protection and its range now overlaps that of feral domestic ferrets (Mustela putorius furo). During this range expansion, European polecats hybridised with feral domestic ferrets producing viable offspring. Here we carry out population-level whole genome sequencing on domestic ferrets, British European polecats, and European polecats from the European mainland and find high degrees of genome introgression in British polecats outside their previous stronghold, even in those individuals phenotyped as pure polecats. We quantify this introgression and find introgressed genes under selection that may assist in cognitive function and sight.

evolutionary biology↗

bioRxiv2021

Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/440778v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@88f5d3org.highwire.dtl.DTLVardef@1c32c71org.highwire.dtl.DTLVardef@9abbedorg.highwire.dtl.DTLVardef@a7f41a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Individualized neoantigen vaccination against mammary carcinoma C_FIG BackgroundHarnessing the immune system to purposely recognize and destroy tumours represents a significant breakthrough in clinical oncology. Nonsynonymous mutations (neoantigenic peptides) were identified as powerful cancer targets. This knowledge can be exploited for further improvements of active immunotherapies, including cancer vaccines as T cells specific for neoantigens are not attenuated by immune tolerance mechanism and do not harm healthy tissues. The current study aimed at developing an optimized multi-target vaccine using short or long neoantigenic peptides utilizing virus-like particles (VLPs) as an efficient vaccine platform. MethodsHere we identified mutations of murine mammary carcinoma cells by integrating mass spectrometry-based immunopeptidomics and whole exome sequencing. Neoantigenic peptides were synthesized and covalently linked to virus-like nanoparticles using a Cu-free click-chemistry method for easy preparation of vaccines against mouse mammary carcinoma. ResultsAs compared to short peptides, vaccination with long peptides was superior in the generation of neoantigen-specific CD4+ and CD8+ T cells which readily produced IFN-{gamma} and TNF-. The resulting anti-tumour effect was associated with favourable immune re-polarization in the tumour microenvironment through reduction of myeloid-derived suppressor cells. Vaccination with long neoantigenic peptides also decreased post-surgical tumour recurrence and metastases, and prolonged mouse survival, despite the tumours low mutational burden. ConclusionIntegrating mass spectrometry-based immunopeptidomics and whole exome-sequencing is an efficient technique for identifying neoantigenic peptides. A multi-target VLP-based vaccine shows a promising anti-tumour results in an aggressive murine mammary carcinoma cell line. Future clinical application using this strategy is readily feasible and practical, as click-chemistry coupling of personalized synthetic peptides to the nanoparticles can be done at the bedside directly before injection.

immunology↗

bioRxiv2020

Free-living psychrophilic bacteria of the genus Psychrobacter are descendents of pathobionts

Host-adapted microbiota are generally thought to have evolved from free-living ancestors. This process is in principle reversible, but examples are few. The genus Psychrobacter (family Moraxellaceae, phylum Gamma-Proteobacteria) includes species inhabiting diverse and mostly polar environments, such as sea ice and marine animals. To probe Psychrobacters evolutionary history, we analyzed 85 Psychrobacter strains by comparative genomics and phenotyping under 24 different growth conditions. Genome-based phylogeny shows Psychrobacter are derived from Moraxella, which are warm-adapted pathobionts. Psychrobacter strains form two ecotypes based on growth temperature: flexible (FE, growth at 4 - 37{degrees}C), and restricted (RE, 4 - 25{degrees}C). FE strains, which can be either phylogenetically basal or derived, have smaller genomes and higher transposon copy numbers. RE strains have larger genomes, and show genomic adaptations towards a psychrophilic lifestyle and are phylogenetically derived only. We then assessed Psychrobacter abundance in 86 mostly wild polar bear stools and tested persistence of select strains in germfree mice. Psychrobacter (both FE and RE) was enriched in stool of polar bears feeding on mammals, but only FE strains persisted in germfree mice. Together these results indicate growth at 37{degrees}C is ancestral in Psychrobacter, lost in many derived species, and likely necessary to colonize the mammalian gut.

microbiology↗

bioRxiv2019

Mass spectrometry based immunopeptidomics leads to robust predictions of phosphorylated HLA class I ligands

The presentation of peptides on class I human leukocyte antigen (HLA-I) molecules plays a central role in immune recognition of infected or malignant cells. In cancer, non-self HLA-I ligands can arise from many different alterations, including non-synonymous mutations, gene fusion, cancer-specific alternative mRNA splicing or aberrant post-translational modifications. Identifying HLA-I ligands remains a challenging task that requires either heavy experimental work for in-vivo identification or optimized bioinformatics tools for accurate predictions. To date, no HLA-I ligand predictor includes post-translational modifications. To fill this gap, we curated phosphorylated HLA-I ligands from several immunopeptidomics studies (including six newly measured samples) covering 72 HLA-I alleles, and retrieved a total of 2,066 unique phosphorylated peptides. We then expanded our motif deconvolution tool to identify precise binding motifs of phosphorylated HLA-I ligands. Our results reveal a clear enrichment of phosphorylated peptides among HLA-C ligands and demonstrate a prevalent role of both HLA-I motifs and kinase motifs on the presentation of phosphorylated peptides. This data further enabled us to develop and validate the first predictor of interactions between HLA-I molecules and phosphorylated peptides.

immunology↗

bioRxiv2019

Integrated Proteogenomic Deep Sequencing and Analytics Accurately Identify Non-Canonical Peptides in Tumor Immunopeptidomes

Efforts to precisely identify tumor human leukocyte antigen (HLA) bound peptides capable of mediating T cell-based tumor rejection still face important challenges. Recent studies suggest that non-canonical tumor-specific HLA peptides that derive from annotated non-coding regions could elicit anti-tumor immune responses. However, sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches are required to robustly identify these non-canonical peptides. We present an MS-based analytical approach that characterizes the non-canonical tumor HLA peptide repertoire, by incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLA peptides and of an immunogenic peptide from a downstream reading frame in the melanoma stem cell marker gene ABCB5. It holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.

cancer biology↗

bioRxiv2019

Deep motif deconvolution of HLA-II peptidomes for robust class II epitope predictions

CD4 T cells are key for priming and regulating immune recognition of infected and cancer cells, but predictions of class II epitopes have limited accuracy. We combined unbiased Mass Spectrometry-based HLA-II peptidomics with a novel motif deconvolution algorithm to profile and analyze a total of 99265 unique HLA-II ligands. Our work demonstrates substantial improvement in the definition of HLA-II binding motifs and enhanced accuracy in class II epitope predictions.

immunology↗

bioRxiv2018

Peptide length distribution and multiple specificity in naturally presented HLA-I ligands

HLA-I molecules bind short peptides and present them for recognition by CD8+ T cells. The length of HLA-I ligands typically ranges from 8 to 12 amino acids, but variability is observed across different HLA-I alleles. Here we collected recent in-depth HLA peptidomics data, including 12 newly generated HLA peptidomes (31,896 unique peptides) from human meningioma samples, to analyze the peptide length distribution and multiple specificity across 84 different HLA-I alleles. We observed a clear clustering of HLA-I alleles with distinct peptide length distributions, which enabled us to study the structural basis of peptide length distributions and predict peptide length distributions from HLA-I sequences. We further identified multiple specificity in several HLA-I molecules and validated these observations with binding assays. Explicitly modeling peptide length distribution and multiple specificity improved predictions of naturally presented HLA-I ligands, as demonstrated in an independent benchmarking based on the new human meningioma samples.

immunology↗