Biology subjects

Guichard, L.

Publications and source records attributed to Guichard, L..

3 recordsLinked to original sources

bioRxiv2024

In-host evolution of Yersinia enterocolitica during a chronic human infection

Following a pacemaker implantation, a 75-years-old patient suffered from five successive bacteremia episodes between in 1999 and 2013 despite long-term antibiotic treatment, with intermittent vegetation apparition on the device atrial lead. Four blood isolates, identified as Yersinia enterocolitica bioserotype 4/O:3, were further genetically and phenotypically characterized. Phylogenetic reconstruction showed that the patient was chronically infected by the same strain, which evolved within the host for 14 years. Single-nucleotide polymorphism (SNP) analysis indicates that the last two isolates evolved in parallel and formed two independent lineages within the host. Pan-genome analysis and genome comparison showed that their common evolution was characterized by 41 small insertion/deletion events, loss of three large DNA fragments and mutations in 140 genes. A phylogenetic analysis by maximum likelihood identified two genes presenting a positive selection signal, suggesting that these mutations provided a survival advantage to bacteria during chronic infection. Quinolone resistance in the last two isolates was acquired through a so far undescribed deletion in the gyrA gene. Mass-spectrometry analysis revealed a strong proteome remodeling in the last two isolates which was correlated with a truncation in the stringent response regulator DksA. A reduced carbon, energy and purine metabolism supports their severe growth defects in vitro. 3rd-generation cephalosporin resistance of the last isolate was correlated with a truncation of OmpF, the main porin translocating antibiotics through the outer-membrane, as well as an increased production of BlaA and AmpC {beta}-lactamases. This is the first report of genetic and phenotypic changes associated to within-host adaptation of a pathogenic Yersinia species under antibiotic pressure.

microbiology↗

bioRxiv2024

Fundamental principles of chromosome organization for meiotic recombination

In meiotic cells, chromosomes are organized as chromatin loop arrays anchored to a protein axis. This organization is essential to regulate meiotic recombination, from DNA double-strand break (DSB) formation to their repair 1. In mammals, it is unknown how chromatin loops are organized along the genome and how proteins participating in DSB formation are tethered to the chromosome axes. Here, we identified three categories of axis-associated genomic sites: PRDM9 binding sites, where DSBs form 2, binding sites of the insulator protein CTCF, and H3K4me3-enriched sites. We demonstrated that PRDM9 promotes the recruitment of MEI4 and IHO1, two proteins essential for DSB formation 3,4. In turn, IHO1 anchors DSB sites to the axis components HORMAD1 and SYCP3. We discovered that IHO1, HORMAD1 and SYCP3 are associated at the DSB ends during DSB repair. Our results highlight how interactions of proteins with specific genomic elements shape the meiotic chromosome organization for recombination.

molecular biology↗

bioRxiv2023

Analysis of a shark reveals ancient habenular asymmetries in gnathostomes and points to Wnt regulation as a driving force in their diversification

The origin of left-right asymmetries in the vertebrate habenula remains largely unknown. Using a transcriptomic approach, we show that in a cartilaginous fish, the catshark Scyliorhinus canicula, habenulae exhibit marked asymmetries both in their medial and their lateral component. Comparisons across gnathostomes suggest that asymmetries in the catshark lateral habenulae reflect an ancestral gnathostome trait, independently lost in tetrapods and neopterygians. Analysis of the mechanisms underlying their formation highlights an essential role of Wnt signaling. Wnt activity is submitted to a dynamic, asymmetric regulation during habenula development, with a Nodal dependent left repression at a stage when precursors for lateral habenulae have exited cell cycles. Pharmacological treatments during this time window reveal that Wnt signaling promotes lateral right neuronal identities in the right lateral habenula, while its repression by Nodal in the left one promotes lateral left neuronal identities. Based on comparisons with the zebrafish and the mouse, we propose that habenular asymmetry formation and diversification in gnathostomes involve the same developmental logic, relying on a conserved temporal regulation of neurogenesis, shaping neuronal identities on both sides, and its modification by a dynamic Wnt activity, right-restricted in the ancestral state and prone to variations in time and space during evolution.

developmental biology↗