Biology subjects

Gomez-Martin, A.

Publications and source records attributed to Gomez-Martin, A..

4 recordsLinked to original sources

bioRxiv2021

Ruminant-associated Listeria monocytogenes isolates belong preferentially to dairy-related hypervirulent clones: a longitudinal study in 19 farms

The increasing prevalence of Listeria monocytogenes infections is a public health issue. Although studies have shown that ruminants constitute reservoirs of this foodborne pathogen, little is known about its epidemiology and genetic diversity within ruminant farms. Here we conducted a large-scale genomic and epidemiologic longitudinal study of Listeria spp. in dairy ruminants and their environments, comprising 19 farms monitored for three consecutive seasons (N=3251 samples). L. innocua was the most prevalent Listeria spp, followed by L. monocytogenes. L. monocytogenes was detected in 52.6% of farms (prevalence in feces samples 3.8%, in farm environment samples 2.5%) and more frequently in cattle (4.1%) and sheep (4.5%) than in goat farms (0.2%). Lineage I accounted for 69% of L. monocytogenes isolates. Among animal samples, the most prevalent sublineages (SL) and clonal complexes (CC) were SL1/CC1, SL219/CC4, SL26/CC26 and SL87/CC87, whereas SL666/CC666 was prevalent in environmental samples. 61 different L. monocytogenes CTs (cgMLST sequence types) were found, 17 of them (27.9%) common to different animals and/or surfaces within the same farms. L. monocytogenes prevalence was not affected by farm hygiene but by season: the overall prevalence of L. monocytogenes in cattle farms was higher during winter, and in sheep farms was higher during winter and spring. Cows in their second lactation had a higher probability of L. monocytogenes fecal shedding than other lactating cows. This study highlights that dairy farms constitute a reservoir for hypervirulent L. monocytogenes and the importance of continuous animal surveillance to reduce the burden of human listeriosis. IMPORTANCEListeria monocytogenes is a bacterial pathogen responsible for listeriosis, the foodborne disease with the highest hospitalization and case-fatality rate. Despite increasing evidence that dairy products and ruminant farms are important reservoirs of L. monocytogenes, little is known about the epidemiology and genetic diversity of Listeria spp. within dairy ruminant farms. We report the largest Listeria spp. longitudinal study in individual domestic animals, and the first using whole-genome sequencing for a deep isolate characterization. Here, we show that domestic ruminants can be asymptomatic carriers of pathogenic Listeria, that L. monocytogenes fecal shedding is often intermittent, and that hypervirulent L. monocytogenes clones are overrepresented in dairy farms. Moreover, we uncover the effect of seasons and lactation number on the prevalence of L. monocytogenes in ruminants. Our study highlights the need for Listeria spp. monitoring in farm animals to control the spread of hypervirulent L. monocytogenes and reduce the burden of human listeriosis.

microbiology↗

bioRxiv2019

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. We meta-analyzed the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (7 studies, N=1700, 344 with any MSDP). We identified 1224 CpGs that were associated with MSDP, of which 341 associated with birth outcomes and 141 associated with gene expression. Only 6 of these CpGs were consistent with the findings from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP associated CpGs were enriched for growth-factor signaling, hormone activity, inflammation, and vascularization, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

genomics↗

bioRxiv2019

LINE-1 retrotransposition impacts the genome of human pre implantation embryos and extraembryonic tissues

Long Interspersed Element 1 (LINE-1/L1) is an abundant retrotransposon that has greatly impacted human genome evolution. LINE-1s are responsible for the generation of millions of insertions in the current human population. The characterization of sporadic cases of mosaic individuals carrying pathogenic L1-insertions, suggest that heritable insertions occurs during early embryogenesis. However, the timing and potential genomic impact of LINE-1 mobilization during early embryogenesis is unknown. Here, we demonstrate that inner cell mass of human pre-implantation embryos support the expression and retrotransposition of LINE -1s. Additionally, we show that LINE-1s are expressed in trophectoderm cells of embryos, and identify placenta-restricted endogenous LINE-1 insertions in newborns. Using human embryonic stem cells as a model of post-implantation epiblast cells, we demonstrate ongoing LINE-1 retrotransposition, which can impact expression of targeted genes. Our data demonstrate that LINE-1 retrotransposition starts very shortly after fertilization and may represent a previously underappreciated factor in human biology and disease.

genomics↗

bioRxiv2016

Neuropilin 1 sequestration by neuropathogenic mutant glycyl-tRNA synthetase is permissive to vascular development and homeostasis

It remains a mystery how dominantly inherited mutations in the housekeeping gene GARS, which encodes glycyl-tRNA synthetase (GlyRS), mediate selective peripheral nerve toxicity resulting in the currently incurable Charcot-Marie-Tooth disease type 2D (CMT2D). A recent study identified the transmembrane receptor protein neuropilin 1 (Nrp1) as a substrate for aberrant extracellular binding of mutant GlyRS. Formation of the Nrp1/mutant GlyRS complex antagonises the interaction of Nrp1 with one of its main natural ligands, vascular endothelial growth factor-A (VEGF-A), contributing to neurodegeneration. Reduced binding of Nrp1 to VEGF-A is known to disrupt blood vessel development and growth. We therefore analysed capillary architecture at early and later symptomatic time points in CMT2D mouse muscles, retina, and sciatic nerve, as well as in embryonic hindbrain. Assessing capillary diameter, density, and branching, we observed no differences between wild-type and mutant animals from embryonic development to three months, spanning the duration over which numerous sensory and neuromuscular phenotypes manifest. This work indicates that mutant GlyRS-mediated disruption of Nrp1/VEGF-A signalling is permissive to capillary maturation and maintenance in CMT2D mice.\n\nSummary StatementAlthough the multi-functional neuropilin 1/VEGF-A signalling pathway is impaired by dominant pathogenic GlyRS variants, the vascular system remains unperturbed in Gars mutant mice.

neuroscience↗