Ehrlichia ruminantium; bacterial life cycle; differential protein expression; endothelial cells; host response; immunomodulation; infection biomarkers; virulence factors
Abstract :
[en] The Rickettsiales Ehrlichia ruminantium, the causal agent of the fatal tick-borne disease Heartwater, induces severe damage to the vascular endothelium in ruminants. Nevertheless, E. ruminantium-induced pathobiology remains largely unknown. Our work paves the way for understanding this phenomenon by using quantitative proteomic analyses (2D-DIGE-MS/MS, 1DE-nanoLC-MS/MS and biotin-nanoUPLC-MS/MS) of host bovine aorta endothelial cells (BAE) during the in vitro bacterium intracellular replication cycle. We detect 265 bacterial proteins (including virulence factors), at all time-points of the E. ruminantium replication cycle, highlighting a dynamic bacterium-host interaction. We show that E. ruminantium infection modulates the expression of 433 host proteins: 98 being over-expressed, 161 under-expressed, 140 detected only in infected BAE cells and 34 exclusively detected in non-infected cells. Cystoscape integrated data analysis shows that these proteins lead to major changes in host cell immune responses, host cell metabolism and vesicle trafficking, with a clear involvement of inflammation-related proteins in this process. Our findings led to the first model of E. ruminantium infection in host cells in vitro, and we highlight potential biomarkers of E. ruminantium infection in endothelial cells (such as ROCK1, TMEM16K, Albumin and PTPN1), which may be important to further combat Heartwater, namely by developing non-antibiotic-based strategies.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Marcelino, Isabel ; CIRAD, UMR ASTRE, F-97170 Petit-Bourg, Guadeloupe, France. ; ASTRE, CIRAD, INRAE, Université de Montpellier (I-MUSE), 34000 Montpellier, France. ; Unité TReD-Path, Institut Pasteur de la Guadeloupe, 97183 Les Abymes, Guadeloupe, France.
Holzmuller, Philippe ; ASTRE, CIRAD, INRAE, Université de Montpellier (I-MUSE), 34000 Montpellier, France. ; CIRAD, UMR ASTRE, 34398 Montpellier, France.
Coelho, Ana ; Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
Mazzucchelli, Gabriel ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.) ; GIGA-Proteomics, B4000 Liege, Belgium.
Fernandez, Bernard; CIRAD, UMR ASTRE, 34398 Montpellier, France.
Vachiéry, Nathalie; CIRAD, UMR ASTRE, F-97170 Petit-Bourg, Guadeloupe, France. ; ASTRE, CIRAD, INRAE, Université de Montpellier (I-MUSE), 34000 Montpellier, France. ; CIRAD, UMR ASTRE, 34398 Montpellier, France.
Language :
English
Title :
Revisiting Ehrlichia ruminantium Replication Cycle Using Proteomics: The Host and the Bacterium Perspectives.
Publication date :
26 May 2021
Journal title :
Microorganisms
eISSN :
2076-2607
Publisher :
MDPI, Basel, Ch
Volume :
9
Issue :
6
Peer reviewed :
Peer Reviewed verified by ORBi
Funding number :
COST action FA-1002/European Commission/; PTDC/CVT/114118/2009/Fundação para a Ciência e a Tecnologia/; PEst-OE/EQB/LA0004/2011/Fundação para a Ciência e a Tecnologia/; EPIGENESIS RegPot European project (n°315988)/European Commission/; FEDER project MALIN2 (2018-FED-1084)/European Commission/
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