PXD010330

PXD010330 is an original dataset announced via ProteomeXchange.

Title	Pathogen and non-pathogen Spotted Fever Group Rickettsia trigger differential proteome signatures in macrophages
Description	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.
HostingRepository	PRIDE
AnnounceDate	2019-02-16
AnnouncementXML	Submission_2019-06-03_01:32:33.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Cátia Santa
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidoethyl-L-cysteine
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-06 02:44:32	ID requested
1	2019-02-15 19:09:57	announced
⏵ 2	2019-06-03 01:32:34	announced	Updated publication reference for PubMed record(s): 30895174.

Curto P, Santa C, Allen P, Manadas B, Sim, õ, es I, Martinez JJ, Trigger Differential Proteome Signatures in Macrophages. Front Cell Infect Microbiol, 9():43(2019) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Rickettsia conorii, Rickettsia montanensis, Spotted fever group Rickettsia, macrophages, SWATH-MS, infection, host-pathogen interactions, metabolic reprogramming, protein processing pathways, proteasome, ER quality control

Bruno Manadas
contact affiliation	Center for Neuroscience and Cell Biology
contact email	bmanadas@gmail.com
lab head
Cátia Santa
contact affiliation	Center for Neuroscience and Cell Biology
contact email	catiajmsanta@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010330
     1. Label: PRIDE project
     2. Name: Pathogen and non-pathogen Spotted Fever Group Rickettsia trigger differential proteome signatures in macrophages