Transcriptomics,Multiomics

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Integrated metabolomics, transcriptomics and proteomics identifies metabolic pathways affected by Anaplasma phagocytophilum infection in tick cells


ABSTRACT: 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 post-genomic 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 for the first time a systems biology integration of metabolomics, transcriptomics and proteomics data to characterize essential metabolic pathways involved in the response of tick cells to A. phagocytophilum infection. 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. 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 tick cell pathways and molecular mechanisms involved in tick-pathogen interactions Two samples with two replicates each were analyzed. Samples included Ixodes scapularis ISE6 cells uninfected (control) and infected with Anaplasma phagocytophilum human NY18 isolate.

ORGANISM(S): Ixodes scapularis  

SUBMITTER: María Moreno  Lourdes Mateos-Hernández   Margarita Villar   Andrés Moreno   Sabine Weisheit   Raquel Tobes   José de la Fuente   Nieves Ayllón   Lesley Bell-Sakyi   Jose De La Fuente   Pilar Alberdi    

PROVIDER: E-GEOD-68881 | ArrayExpress| 2016-01-17

SECONDARY ACCESSION(S): SRP058346GSE68881PRJNA283969

REPOSITORIES: GEO, ArrayExpress, ENA

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Integrated Metabolomics, Transcriptomics and Proteomics Identifies Metabolic Pathways Affected by Anaplasma phagocytophilum Infection in Tick Cells.

Villar Margarita M   Ayllón Nieves N   Alberdi Pilar P   Moreno Andrés A   Moreno María M   Tobes Raquel R   Mateos-Hernández Lourdes L   Weisheit Sabine S   Bell-Sakyi Lesley L   de la Fuente José J  

Molecular & cellular proteomics : MCP 20150930 12


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  ...[more]

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