Dataset Information

Pathogen and non-pathogen Spotted Fever Group Rickettsia trigger differential proteome signatures in macrophages

ABSTRACT: We have previously reported that Rickettsia conorii and Rickettsia montanensis have distinct intracellular fates within THP-1 macrophages, suggesting that the ability to proliferate within macrophages may be a distinguishable factor between pathogenic and non-pathogenic Spotted fever group (SFG) members. To start unraveling the molecular mechanisms underlying the capacity (or not) of SFG Rickettsia to establish their replicative niche in macrophages, we have herein profiled the host proteomic alterations resulted by the infection of THP-1 macrophages with R. conorii and R. montanensis using a high throughput quantitative proteomics approach (SWATH-MS). Our results revealed that these two members of SFG Rickettsia with distinct pathogenicity attributes for humans, trigger differential proteomic signatures in macrophage-like cells. Although infection by both rickettsial species resulted in a lower abundance of enzymes of glycolysis and pentose phosphate pathway, the pathogenic R. conorii specifically induced the accumulation of several enzymes of the tricarboxylic acid cycle, oxidative phosphorylation, fatty acid -oxidation and glutaminolysis, as well as of several inner and outer membrane mitochondrial transporters. These results suggest a profound metabolic rewriting of macrophages by R. conorii towards a metabolic signature of an M2-like (anti-inflammatory) activation program. Moreover, our results revealed that several subunits forming the proteasome and immunoproteasome are found in lower abundance upon infection with both rickettsial species, which may help bacteria to escape immune surveillance. Remarkably, R. conorii-infection specifically induced the accumulation of several host proteins implicated in protein processing and quality control in ER, suggesting that this pathogenic Rickettsia may be able to compensate the accumulation of misfolded proteins by increasing the ER protein folding capacity and subsequently restore host cell homeostasis. This work reveals novel aspects of macrophage-Rickettsia interactions, expanding our knowledge of how pathogenic rickettsiae explore host cells to their advantage.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Spotted Fever Group Homo Sapiens (human)

TISSUE(S): Cell Culture, Macrophage

SUBMITTER: Cátia Santa

LAB HEAD: Bruno Manadas

PROVIDER: PXD010330 | Pride | 2019-02-16

REPOSITORIES: Pride

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A Pathogen and a Non-pathogen Spotted Fever Group Rickettsia Trigger Differential Proteome Signatures in Macrophages.

Curto Pedro P Santa Cátia C Allen Paige P Manadas Bruno B Simões Isaura I Martinez Juan J JJ

Frontiers in cellular and infection microbiology 20190306

We have previously reported that Rickettsia conorii and Rickettsia montanensis have distinct intracellular fates within THP-1 macrophages, suggesting that the ability to proliferate within macrophages may be a distinguishable factor between pathogenic and non-pathogenic Spotted fever group (SFG) members. To start unraveling the molecular mechanisms underlying the capacity (or not) of SFG Rickettsia to establish their replicative niche in macrophages, we have herein used quan ...[more]

PMID: 30895174

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Project description:Rationale: Epicardial adipose tissue (EAT) has been independently associated with non-calcified, high-risk coronary plaques in low-to intermediate risk subjects. Recently, a bidirectional communication was shown between EAT and diseased coronary arteries. In high-risk patients it is unknown whether quantitative measures of EAT can capture, and which molecular players are involved in this mutual interplay. Objective: In a high-risk population, we aimed to determine how the volume of EAT is linked to coronary artery disease (CAD) and to identify potential EAT-deregulated pathways in CAD patients specifically related to coronary artery calcification (CAC). Methods and Results: In a prospective cohort of 574 degenerative severe aortic stenosis patients referred to cardiac surgery, we quantified fat depots by computed tomography (CT) and performed a comparative quantitative proteomics of thoracic fat, including EAT, mediastinal (MAT) and subcutaneous (SAT) adipose tissues. We did not find an independent association of EAT volume with the severity, distribution and complexity of coronary stenosis in invasive coronary angiography. Although, EAT volume was correlated with high CAC, its cardiovascular risk factors-adjusted association was not significant. Taking as reference non-CAD matched-patients and compared to MAT and SAT, EAT proteomic signature of CAD was characterized by up-regulation of pro-calcifying annexins (Annexin A2, ANXA2), fatty acid binding transporters (FABP4) and inflammatory signaling proteins, and by down-regulation of fetuin-A and redox state regulatory enzymes. In EAT, ANXA2 regulation was positively correlated with CAC. EAT gene expression studies confirmed overexpression of ANXA2 and FABP4 in CAD, but no expression of FETUA was detected. Compared with non-CAD, fetuin-A circulating levels were higher in CAD, whereas no fetuin-A pericardial fluid differences were found. Conclusions: In this high-risk cohort, EAT presented an imbalance of pro-calcifying, pro-inflammatory and lipid transporters mediators. These local EAT-mediated regulatory mechanisms were not reflected by the CT volume of EAT alone.

Project description:Fresh fish are highly perishable food products and their short shelf-life limits their commercial exploitation, leads to waste and has a negative impact on aquaculture sustainability. New non-thermal food processing methods, such as High pressure (HP), are being investigated to prolong shelf-life while assuring high food quality. We applied several tools to evaluate the impacts of HP processing on European sea bass (Dicentrarchus labrax) fillets quality and shelf life. The data here presented includes visual and physical measurements of flesh quality and the microbiome and proteome profiles of control and HP-processed sea bass fillets (600MPa, 25ºC, 5min), after isothermal storage (2°C) for different periods ranging from 1 to 67 days. Color (L-, a- and b- values) change and texture (hardness, cohesiveness and adhesiveness) parameters were obtained by using appropriate colorimeter and texture analyser, respectively, during refrigerated storage. Bacterial diversity was analysed by Illumina high-throughput sequencing of the 16S rRNA gene in five pooled DNAs from control or HP-processed fillets after 1, 11 or 67 days and the raw reads were deposited in the NCBI-SRA database with accession number PRJNA517618. In addition, high-throughput sequencing of the internal transcribed spacer (ITS) region targeting yeast and moulds was run for control or HP-processed fillets at the end of storage (11 or 67 days, respectively), being deposited under SRA accession PRJNA517779. Quantitative label-free proteomics profiles were analysed by SWATH-MS (Sequential Windowed data independent Acquisition of the Total High-resolution-Mass Spectra) in myofibrillar or sarcoplasmic enriched protein extracts pooled for control or HP-processed filets after short (1d) or long-term (11-67 days) storage. These data support the findings reported in “High pressure processing of European sea bass (Dicentrarchus labrax) fillets and tools for flesh quality and shelf life monitoring” (Tsironi et al. 2019).

			Action	DRS
	CT_B1_1.wiff	Wiff
	CT_B1_1.wiff.scan	Wiff
	CT_B1_2.wiff	Wiff
	CT_B1_2.wiff.scan	Wiff
	CT_B2_1.wiff	Wiff

Dataset Information

Pathogen and non-pathogen Spotted Fever Group Rickettsia trigger differential proteome signatures in macrophages

Dataset's files

Publications

A Pathogen and a Non-pathogen Spotted Fever Group <i>Rickettsia</i> Trigger Differential Proteome Signatures in Macrophages.

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