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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Integrated genomics of Crohn’s disease risk variant identifies a role for CLEC12A in antibacterial autophagy

ABSTRACT: Using integrated genomics we identify a role for CLEC12A in antibacterial autophagy. Clec12a-/- mice are more susceptible to bacterial infection and CLEC12A deficient cells exhibit impaired antibacterial autophagy. We used transcriptional profilinf to understand the role of CLEC12A in the response to Salmonella and Listeria. Bone marrow-derived macrophages from WT or Clec12a-/- mice were infected with Salmonella enterica serovar Typhimurium or Listeria monocytogenes. Cells were harvested at 0,3,6, and 24hours post-infection for RNA analysis. Please note that single-end sequencing was performed but two files: R1 files that contained the sample barcodes (19 or 17bp reads) and R2 files that contained the single-end-sequenced 46bp cDNA reads were generated. Since the barcode info is mostly redundant, only R2 reads were submitted (described in 'raw_file_readme.txt').

ORGANISM(S): Mus musculus

SUBMITTER: Ramnik Xavier

PROVIDER: E-GEOD-69132 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Integrated genomics of Crohn’s disease risk variant identifies a role for CLEC12A in antibacterial autophagy

Project description:Using integrated genomics we identify a role for CLEC12A in antibacterial autophagy. Clec12a-/- mice are more susceptible to bacterial infection and CLEC12A deficient cells exhibit impaired antibacterial autophagy. We used transcriptional profilinf to understand the role of CLEC12A in the response to Salmonella and Listeria.

2015-06-30 | GSE69132 | GEO

Scheidel2016 - In Silico Knockout Studies of Xenophagy Capturing of Salmonella

Project description:Xenophagy, also known as antibacterial autophagy, is a process of capturing and eliminating cytosolic pathogens, like Salmonella. Salmonella is the best-studied model organism for xenophagy. We present a Petri net model of Salmonella xenophagy in epithelial cells. The model is based on functional information derived from literature data and contains all known processes of Salmonella xenophagy in epithelial. The model comprises the molecular mechanism of galectin-8-dependent and ubiquitin-dependent autophagy, including regulatory processes, like nutrient-dependent regulation of autophagy and TBK1-dependent activation of the autophagy receptor, OPTN. To model the activation of TBK1, we proposed a mechanism of TBK1 activation, suggesting a spatial and temporal regulation of this process. The Petri net is connected, covered by T-invariants, and each T-invariant has a meaningful biological interpretation. We checked the model structure for consistencies and correctness. We found 16 basic functional modules, which describe different pathways of the autophagic capturing of Salmonella and reflect the basic dynamics of the system. The PN model of Salmonella xenophagy comprises 61 places, including nine logical places, and 69 transitions connected by 184 arcs.

2020-04-09 | MODEL1904150001 | BioModels

In-vitro evaluation of Pseudomonas fluorescens antibacterial activity against Listeria spp. isolated from New Zealand horticultural environments

Project description:Beneficial bacteria with antibacterial properties are an attractive alternative to chemical-based antibacterial or bactericidal agents. The aim of our study was to source such bacteria from horticultural produce and environments and to explore the mechanisms of their antimicrobial properties. Four strains of Pseudomonas fluorescens were isolated that possessed antibacterial activity against the pathogen Listeria monocytogenes.

2023-03-10 | PXD019965 | Pride

CD44a functions as a regulator of p53 signaling, apoptosis and autophagy in the antibacterial immune response

Project description:CD44 is a transmembrane adhesion molecule and the major receptor for hyaluronan. The function of CD44 has been implicated in numerous biological processes. Our study finds that zebrafish CD44a variants function as positive regulators in antibacterial response. In order to reveal the possible antibacterial mechanism of CD44a, the wild-type and CD44a-/--14del zebrafish larvaes infected with E. piscicida collected at 24 and 48 hpi were used for transcriptome sequencing. Our data demonstrate that zebrafish CD44a functions as a regulator of p53 signaling, apoptosis and autophagy in the antibacterial immune response.

2021-07-26 | GSE180770 | GEO

An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity.

Project description:Type I interferons were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of interferon antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of interferon-induced antiviral activity. Here we identify a novel role for RNase-L in the host antibacterial response. RNase-L-/- mice exhibited a dramatic increase in mortality following challenge with Bacillus anthracis and Escherichia coli; this increased susceptibility was due to a compromised immune response resulting in increased bacterial load. Investigation of the mechanisms of RNase-L antibacterial activity indicated that RNase-L is required for the optimal induction of proinflammatory cytokines that play essential roles in host defense from bacterial pathogens. RNase-L also regulated the expression of the endolysosomal protease, cathepsin-E, and endosome-associated activities, that function to eliminate internalized bacteria and may contribute to RNase-L antimicrobial action. Our results reveal a unique role for RNase-L in the antibacterial response that is mediated through multiple mechanisms. As a regulator of fundamental components of the innate immune response, RNase-L represents a viable therapeutic target to augment host defense against diverse microbial pathogens. two strains: wildtype and knockout, three time points: untreated, 2hours, and 8hours. three replication for each group. Totally 18 samples.

2008-12-19 | E-GEOD-13530 | biostudies-arrayexpress

Mycobacterium tuberculosis H37Rv transcriptional response to antibacterial agents

Project description:Bacteria commonly adapt to stresses by altering gene expression. To understand the response of M. tuberculosis (MTB) to various antibacterial agents, we performed transcriptomics on MTB bacilli exposed to several test compounds as well as known drugs (capreomycin, cycloserine, ethionamide, isoniazid, kanamycin, moxifloxacin, PA-824, rifampicin, streptomycin). Bacteria were exposed for 16 hrs to various concentrations of each drug (different multiples of the compound's MIC), as noted in the title of each sample. RNA was isolated and applied to arrays provided by TIGR under the NIAID contract N01-AI-15447

2015-11-11 | E-GEOD-71200 | biostudies-arrayexpress

Mycobacterium tuberculosis H37Rv transcriptional response to antibacterial agents

2015-11-11 | GSE71200 | GEO

An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity.

2008-12-19 | GSE13530 | GEO

Transcriptomics analysis reveals the molecular mechanisms of the antibacterial activity of gallium nitrate against Acinetobacter baumannii isolated from bloodstream infections

Project description:Purpose: The aim of this study was to explore the antibacterial effect and molecular mechanism of gallium nitrate [Ga(NO 3 ) 3 ] against Acinetobacter baumannii from bloodstream infection. Methods: A total of 40 A. baumannii with different antimicrobials susceptibility patterns were isolated from bloodstream infections. In vitro antibacterial effect of Ga(NO 3 ) 3 was analyzed by micro-dilution method and time-kill assay. The effect of ferric chloride/heme on the antibacterial effect of Ga(NO 3 ) 3 was evaluated. Transcriptome sequencing was performed to elucidate the antibacterial mechanism of gallium nitrate. Mouse infection model was conducted to explore the in vivo efficacy of gallium nitrate . Results: Ga(NO 3 ) 3 exhibited excellent antibacterial effect in RPMI 1 640 medium containing 10% human serum (MICs ranged from 0.06 μg/mL to 0.125 μg/mL), whereas its antibacterial effect was weakened by exogenous ferric chloride/heme. Ga(NO 3 ) 3 inhibited A. baumannii growth in a dose- and time- dependent manner. Ga(NO 3 ) 3 exerted antibacterial effect by up-regulating the expression of genes associated with biosynthesis and transport of siderophore and disrupting multiple iron dependent metabolism processes. Ga(NO 3 ) 3 significantly reduced bacterial load in the neutropenic mouse thigh infection model. Conclusions: This study revealed that Ga(NO 3 ) 3 had excellent antibacterial activity both in vivo and in vitro . It might be a potential drug for treating bloodstream infections of A. baumannii

2022-01-27 | GSE194255 | GEO

An OMIC approach to elaborate the antibacterial mechanisms of different alkaloids

Project description:In the current study, RNA sequencing was used to comparatively elaborate the activities and the effects of the alkaloids, boldine, bulbocapnine, and roemerine along with the well-known antibacterial alkaloid berberine on Bacillus subtilis cells.

2018-07-17 | GSE104946 | GEO

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