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Villar M.,Institute Investigacion en Recursos Cinege ticos IREC CSIC UCLM JCCM | Ayllon N.,Institute Investigacion en Recursos Cinege ticos IREC CSIC UCLM JCCM | Alberdi P.,Institute Investigacion en Recursos Cinege ticos IREC CSIC UCLM JCCM | Moreno A.,University of Castilla - La Mancha | And 9 more authors.
Molecular and Cellular Proteomics | Year: 2015

Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human granulocytic anaplasmosis. These intracellular bacteria establish infection by affecting cell function in both the vertebrate host and the tick vector, Ixodes scapularis. Previous studies have characterized the tick transcriptome and proteome in response to A. phagocytophilum infection. However, in the postgenomic era, the integration of omics datasets through a systems biology approach allows network-based analyses to describe the complexity and functionality of biological systems such as host-pathogen interactions and the discovery of new targets for prevention and control of infectious diseases. This study reports the first systems biology integration of metabolomics, transcriptomics, and proteomics data to characterize essential metabolic pathways involved in the tick response to A. phagocytophilum infection. The ISE6 tick cells used in this study constitute a model for hemocytes involved in pathogen infection and immune response. The results showed that infection affected protein processing in endoplasmic reticulum and glucose metabolic pathways in tick cells. These results supported tick-Anaplasma co-evolution by providing new evidence of how tick cells limit pathogen infection, while the pathogen benefits from the tick cell response to establish infection. Additionally, ticks benefit from A. phagocytophilum infection by increasing survival while pathogens guarantee transmission. The results suggested that A. phagocytophilum induces protein misfolding to limit the tick cell response and facilitate infection but requires protein degradation to prevent ER stress and cell apoptosis to survive in infected cells. Additionally, A. phagocytophilum may benefit from the tick cell's ability to limit bacterial infection through PEPCK inhibition leading to decreased glucose metabolism, which also results in the inhibition of cell apoptosis that increases infection of tick cells. These results support the use of this experimental approach to systematically identify cell pathways and molecular mechanisms involved in tick-pathogen interactions. Data are available via ProteomeXchange with identifier PXD002181. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Source

Doncel-Perez E.,University of Castilla - La Mancha | Mateos-Hernandez L.,Institute Investigacion en Recursos Cinegeticos IRECCSIC UCLM JCCM | Pareja E.,Oh No Sequences Research Group | Garcia-Forcada A.,University of Castilla - La Mancha | And 8 more authors.
Journal of Immunology | Year: 2016

Guillain-Barre syndrome (GBS) is an immune-mediated peripheral neuropathy. The goal of this research was the identification of biomarkers associated with recovery from GBS. In this study, we compared the transcriptome of PBMCs from a GBS patient and her healthy twin to discover possible correlates of disease progression and recovery. The study was then extended using GBS and spinal cord injury unrelated patients with similar medications and healthy individuals. The early growth response gene-2 (EGR2) was upregulated in GBS patients during disease recovery. The results provided evidence for the implication of EGR2 in GBS and suggested a role for EGR2 in the regulation of IL-17, IL-22, IL-28A, and TNF-b cytokines in GBS patients. These results identified biomarkers associated with GBS recovery and suggested that EGR2 overexpression has a pivotal role in the downregulation of cytokines implicated in the pathophysiology of this acute neuropathy. © 2016 by The American Association of Immunologists, Inc. Source

de la Fuente J.,Institute Investigacion en Recursos Cinegeticos IREC CSIC UCLM JCCM | de la Fuente J.,Oklahoma State University | Diez-Delgado I.,Institute Investigacion en Recursos Cinegeticos IREC CSIC UCLM JCCM | Diez-Delgado I.,Complutense University of Madrid | And 16 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly affect humans and animals worldwide. The life cycle of mycobacteria is complex and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Recently, comparative genomics analyses have provided new insights into the evolution and adaptation of the MTBC to survive inside the host. However, most of this information has been obtained using M. tuberculosis but not other members of the MTBC such as M. bovis and M. caprae. In this study, the genome of three M. bovis (MB1, MB3, MB4) and one M. caprae (MB2) field isolates with different lesion score, prevalence and host distribution phenotypes were sequenced. Genome sequence information was used for whole-genome and protein-targeted comparative genomics analysis with the aim of finding correlates with phenotypic variation with potential implications for tuberculosis (TB) disease risk assessment and control. At the whole-genome level the results of the first comparative genomics study of field isolates of M. bovis including M. caprae showed that as previously reported for M. tuberculosis, sequential chromosomal nucleotide substitutions were the main driver of the M. bovis genome evolution. The phylogenetic analysis provided a strong support for the M. bovis/M. caprae clade, but supported M. caprae as a separate species. The comparison of the MB1 and MB4 isolates revealed differences in genome sequence, including gene families that are important for bacterial infection and transmission, thus highlighting differences with functional implications between isolates otherwise classified with the same spoligotype. Strategic protein-targeted analysis using the ESX or type VII secretion system, proteins linking stress response with lipid metabolism, host T cell epitopes of mycobacteria, antigens and peptidoglycan assembly protein identified new genetic markers and candidate vaccine antigens that warrant further study to develop tools to evaluate risks for TB disease caused by M. bovis/M.caprae and for TB control in humans and animals. © 2015 de la Fuente et al. Source

Contreras M.,Institute Investigacion en Recursos Cinegeticos IREC CSIC UCLM JCCM | de la Fuente J.,Institute Investigacion en Recursos Cinegeticos IREC CSIC UCLM JCCM | de la Fuente J.,Oklahoma State University | Estrada-Pena A.,University of Zaragoza | And 3 more authors.
Molecular Ecology Resources | Year: 2014

This article documents the public availability of a global transcriptome comparison between Lyme disease tick vectors, Ixodes scapularis and Ixodes ricinus. © 2014 John Wiley & Sons Ltd. Source

Ouma W.Z.,Ohio State University | Mejia-Guerra M.K.,Ohio State University | Yilmaz A.,Yildiz Technical University | Pareja-Tobes P.,Oh No Sequences Research Group | And 3 more authors.
Scientific Reports | Year: 2015

Establishing the architecture of gene regulatory networks (GRNs) relies on chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) methods that provide genome-wide transcription factor binding sites (TFBSs). ChIP-Seq furnishes millions of short reads that, after alignment, describe the genome-wide binding sites of a particular TF. However, in all organisms investigated an average of 40% of reads fail to align to the corresponding genome, with some datasets having as much as 80% of reads failing to align. We describe here the provenance of previously unaligned reads in ChIP-Seq experiments from animals and plants. We show that a substantial portion corresponds to sequences of bacterial and metazoan origin, irrespective of the ChIP-Seq chromatin source. Unforeseen was the finding that 30%-40% of unaligned reads were actually alignable. To validate these observations, we investigated the characteristics of the previously unaligned reads corresponding to TAL1, a human TF involved in lineage specification of hemopoietic cells. We show that, while unmapped ChIP-Seq read datasets contain foreign DNA sequences, additional TFBSs can be identified from the previously unaligned ChIP-Seq reads. Our results indicate that the re-evaluation of previously unaligned reads from ChIP-Seq experiments will significantly contribute to TF target identification and determination of emerging properties of GRNs. © 2015, Nature Publishing Group. All rights reserved. Source

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