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Article ; Online: Modulation of the E-cadherin in human cells infected in vitro with Coxiella burnetii.

Omar Osman, Ikram / Mezouar, Soraya / Brahim-Belhaouari, Djamal / Mege, Jean-Louis / Devaux, Christian Albert

2023 Volume 18, Issue 6, Page(s) e0285577

Abstract: High concentration of soluble E-cadherin (E-cad) was previously found in sera from Q fever patients. Here, BeWo cells which express a high concentration of E-cad were used as an in vitro model to investigate the expression and function of E-cad in ... ...

Abstract	High concentration of soluble E-cadherin (E-cad) was previously found in sera from Q fever patients. Here, BeWo cells which express a high concentration of E-cad were used as an in vitro model to investigate the expression and function of E-cad in response to infection by Coxiella burnetii, the etiological agent of Q fever. Infection of BeWo cells with C. burnetii leads to a decrease in the number of BeWo cells expressing E-cad at their membrane. A shedding of soluble E-cad was associated with the post-infection decrease of membrane-bound E-cad. The modulation of E-cad expression requires bacterial viability and was not found with heat-inactivated C. burnetii. Moreover, the intracytoplasmic cell concentration of β-catenin (β-cat), a ligand of E-cad, was reduced after bacterial infection, suggesting that the bacterium induces modulation of the E-cad/β-cat signaling pathway and CDH1 and CTNNB1 genes transcription. Finally, several genes operating the canonical Wnt-Frizzled/β-cat pathway were overexpressed in cells infected with C. burnetii. This was particularly evident with the highly virulent strain of C. burnetii, Guiana. Our data demonstrate that infection of BeWo cells by live C. burnetii modulates the E-cad/β-cat signaling pathway.
MeSH term(s)	Humans ; Coxiella burnetii ; Q Fever/microbiology ; Cadherins/genetics ; Cadherins/metabolism
Chemical Substances	Cadherins
Language	English
Publishing date	2023-06-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0285577
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Identification and Characterization of an HtrA Sheddase Produced by

Osman, Ikram Omar / Caputo, Aurelia / Pinault, Lucile / Mege, Jean-Louis / Levasseur, Anthony / Devaux, Christian A

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: Having previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells ... ...

Abstract	Having previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells by
MeSH term(s)	Humans ; Coxiella burnetii/enzymology ; Coxiella burnetii/genetics ; Coxiella burnetii/pathogenicity ; Interleukin-10/metabolism ; Macrophages/microbiology ; Q Fever/microbiology ; Q Fever/physiopathology ; THP-1 Cells/microbiology ; Cadherins/metabolism ; Genome, Bacterial/genetics ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Gene Expression Regulation, Bacterial ; Recombinant Proteins/genetics ; Host Microbial Interactions ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Escherichia coli/genetics
Chemical Substances	Interleukin-10 (130068-27-8) ; DegP protease (EC 3.4.21.-) ; Cadherins ; Bacterial Proteins ; Recombinant Proteins ; Serine Endopeptidases (EC 3.4.21.-)
Language	English
Publishing date	2023-06-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241310904
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19

Clemence, Garrec / Jeffrey, Arrindell / Jonatane, Andrieu / Mege, Jean-Louis / Omar Osman, Ikram / Devaux, Christian A.

bioRxiv

Abstract: SARS-CoV-2 can infect different organs, including the intestine. In Caco-2 intestinal cell line, SARS-CoV-2 modulates the ACE2 receptor expression and affects the expression of molecules involved in intercellular junctions. To further explore the ... ...

Abstract	SARS-CoV-2 can infect different organs, including the intestine. In Caco-2 intestinal cell line, SARS-CoV-2 modulates the ACE2 receptor expression and affects the expression of molecules involved in intercellular junctions. To further explore the possibility that the intestinal epithelium serves as an alternative infection route for SARS-CoV-2, we used a model of polarised intestinal cell monolayers grown on the polycarbonate membrane of Transwell inserts, inoculated with the virus either in the upper or lower chamber of culture. In both polarised Caco-2 cell monolayers and co-culture Caco-2/HT29 cell monolayer, apical SARS-CoV-2 inoculation was found to be much more effective in establishing infection than basolateral inoculation. In addition, apical SARS-CoV-2 infection triggers monolayer degeneration, as shown by histological examination, measurement of trans-epithelial electronic resistance, and cell adhesion molecule expression. During this process, the infectious viruses reach the lower chamber, suggesting either a transcytosis mechanism from the apical side to the basolateral side of cells, a paracellular trafficking of the virus after damage to intercellular junctions in the epithelial barrier, or both. Taken together, these data highlight a preferential tropism of SARS-CoV-2 for the apical side of the human intestinal tract and suggests that infection via the intestinal lumen leads to a systemic infection.
Keywords	covid19
Language	English
Publishing date	2024-01-09
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.01.08.574642
Database	COVID19

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Article ; Online: Modulation of the E-cadherin in human cells infected in vitro with Coxiella burnetii.

Ikram Omar Osman / Soraya Mezouar / Djamal Brahim-Belhaouari / Jean-Louis Mege / Christian Albert Devaux

PLoS ONE, Vol 18, Iss 6, p e

2023 Volume 0285577

Abstract	High concentration of soluble E-cadherin (E-cad) was previously found in sera from Q fever patients. Here, BeWo cells which express a high concentration of E-cad were used as an in vitro model to investigate the expression and function of E-cad in response to infection by Coxiella burnetii, the etiological agent of Q fever. Infection of BeWo cells with C. burnetii leads to a decrease in the number of BeWo cells expressing E-cad at their membrane. A shedding of soluble E-cad was associated with the post-infection decrease of membrane-bound E-cad. The modulation of E-cad expression requires bacterial viability and was not found with heat-inactivated C. burnetii. Moreover, the intracytoplasmic cell concentration of β-catenin (β-cat), a ligand of E-cad, was reduced after bacterial infection, suggesting that the bacterium induces modulation of the E-cad/β-cat signaling pathway and CDH1 and CTNNB1 genes transcription. Finally, several genes operating the canonical Wnt-Frizzled/β-cat pathway were overexpressed in cells infected with C. burnetii. This was particularly evident with the highly virulent strain of C. burnetii, Guiana. Our data demonstrate that infection of BeWo cells by live C. burnetii modulates the E-cad/β-cat signaling pathway.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Coxiella burnetii

Devaux, Christian A / Osman, Ikram Omar / Million, Matthieu / Raoult, Didier

Frontiers in veterinary science

2020 Volume 7, Page(s) 558481

Abstract: The "One Health" concept recognizes that human health is connected to animal health and to the ecosystems. ...

Abstract	The "One Health" concept recognizes that human health is connected to animal health and to the ecosystems.
Language	English
Publishing date	2020-11-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2020.558481
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2?

Devaux, Christian A / Pinault, Lucile / Osman, Ikram Omar / Raoult, Didier

Frontiers in public health

2021 Volume 8, Page(s) 608765

Abstract: A novel severe acute respiratory syndrome coronavirus, SARS-CoV-2, emerged in China in December 2019 and spread worldwide, causing more than 1.3 million deaths in 11 months. Similar to the human SARS-CoV, SARS-CoV-2 shares strong sequence homologies with ...

Abstract	A novel severe acute respiratory syndrome coronavirus, SARS-CoV-2, emerged in China in December 2019 and spread worldwide, causing more than 1.3 million deaths in 11 months. Similar to the human SARS-CoV, SARS-CoV-2 shares strong sequence homologies with a sarbecovirus circulating in
MeSH term(s)	Animals ; COVID-19/immunology ; COVID-19/pathology ; China ; Chiroptera/virology ; Genetic Predisposition to Disease ; Host Specificity/genetics ; Humans ; Ophiophagus hannah/virology ; Pandemics ; Pangolins/virology ; Polymorphism, Single Nucleotide ; Receptors, Angiotensin/genetics ; Replication Origin ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity
Chemical Substances	Receptors, Angiotensin
Language	English
Publishing date	2021-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2020.608765
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2?

Christian A. Devaux / Lucile Pinault / Ikram Omar Osman / Didier Raoult

Frontiers in Public Health, Vol

2021 Volume 8

Abstract	A novel severe acute respiratory syndrome coronavirus, SARS-CoV-2, emerged in China in December 2019 and spread worldwide, causing more than 1.3 million deaths in 11 months. Similar to the human SARS-CoV, SARS-CoV-2 shares strong sequence homologies with a sarbecovirus circulating in Rhinolophus affinis bats. Because bats are expected to be able to transmit their coronaviruses to intermediate animal hosts that in turn are a source of viruses able to cross species barriers and infect humans (so-called spillover model), the identification of an intermediate animal reservoir was the subject of intense researches. It was claimed that a reptile (Ophiophagus hannah) was the intermediate host. This hypothesis was quickly ruled out and replaced by the pangolin (Manis javanica) hypothesis. Yet, pangolin was also recently exonerated from SARS-CoV-2 transmission to humans, leaving other animal species as presumed guilty. Guided by the spillover model, several laboratories investigated in silico the species polymorphism of the angiotensin I converting enzyme 2 (ACE2) to find the best fits with the SARS-CoV-2 spike receptor-binding site. Following the same strategy, we used multi-sequence alignment, 3-D structure analysis, and electrostatic potential surface generation of ACE2 variants to predict their binding capacity to SARS-CoV-2. We report evidence that such simple in silico investigation is a powerful tool to quickly screen which species are potentially susceptible to SARS-CoV-2. However, possible receptor binding does not necessarily lead to successful replication in host. Therefore, we also discuss here the limitations of these in silico approaches in our quest on the origins of COVID-19 pandemic.
Keywords	COVID-19 ; SARS-CoV-2 ; coronavirus ; ACE2 ; in silico analyses ; Public aspects of medicine ; RA1-1270
Subject code	590
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification and Characterization of an HtrA Sheddase Produced by Coxiella burnetii

Ikram Omar Osman / Aurelia Caputo / Lucile Pinault / Jean-Louis Mege / Anthony Levasseur / Christian A. Devaux

International Journal of Molecular Sciences, Vol 24, Iss 10904, p

2023 Volume 10904

Abstract: Having previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells by C. burnetii leads to modulation of the E-cad/β-cat pathway, our purpose was to identify which sheddase(s) might catalyze the ...

Abstract	Having previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells by C. burnetii leads to modulation of the E-cad/β-cat pathway, our purpose was to identify which sheddase(s) might catalyze the cleavage of E-cad. Here, we searched for a direct mechanism of cleavage initiated by the bacterium itself, assuming the possible synthesis of a sheddase encoded in the genome of C. burnetii or an indirect mechanism based on the activation of a human sheddase. Using a straightforward bioinformatics approach to scan the complete genomes of four laboratory strains of C. burnetii , we demonstrate that C. burnetii encodes a 451 amino acid sheddase (CbHtrA) belonging to the HtrA family that is differently expressed according to the bacterial virulence. An artificial CbHtrA gene (CoxbHtrA) was expressed, and the CoxbHtrA recombinant protein was found to have sheddase activity. We also found evidence that the C. burnetii infection triggers an over-induction of the human HuHtrA gene expression. Finally, we demonstrate that cleavage of E-cad by CoxbHtrA on macrophages-THP-1 cells leads to an M2 polarization of the target cells and the induction of their secretion of IL-10, which “disarms” the target cells and improves C. burnetii replication. Taken together, these results demonstrate that the genome of C . burnetii encodes a functional HtrA sheddase and establishes a link between the HtrA sheddase-induced cleavage of E-cad, the M2 polarization of the target cells and their secretion of IL-10, and the intracellular replication of C. burnetii .
Keywords	Q fever ; Coxiella burnetii ; HtrA ; sheddase ; E-cadherin ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19

Garrec, Clémence / Arrindell, Jeffrey / Andrieu, Jonatane / Desnues, Benoit / Mege, Jean-Louis / Osman, Ikram Omar / Devaux, Christian A.

bioRxiv

Abstract	SARS-CoV-2 can infect different organs, including the intestine. In Caco-2 intestinal cell line, SARS-CoV-2 modulates the ACE2 receptor expression and affects the expression of molecules involved in intercellular junctions. To further explore the possibility that the intestinal epithelium serves as an alternative infection route for SARS-CoV-2, we used a model of polarised intestinal cell monolayers grown on the polycarbonate membrane of Transwell inserts, inoculated with the virus either in the upper or lower chamber of culture. In both polarised Caco-2 cell monolayers and co-culture Caco-2/HT29 cell monolayer, apical SARS-CoV-2 inoculation was found to be much more effective in establishing infection than basolateral inoculation. In addition, apical SARS-CoV-2 infection triggers monolayer degeneration, as shown by histological examination, measurement of trans-epithelial electronic resistance, and cell adhesion molecule expression. During this process, the infectious viruses reach the lower chamber, suggesting either a transcytosis mechanism from the apical side to the basolateral side of cells, a paracellular trafficking of the virus after damage to intercellular junctions in the epithelial barrier, or both. Taken together, these data highlight a preferential tropism of SARS-CoV-2 for the apical side of the human intestinal tract and suggests that infection via the intestinal lumen leads to a systemic infection.
Keywords	covid19
Language	English
Publishing date	2024-01-09
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.01.08.574642
Database	COVID19

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Article ; Online: Coxiella burnetii in Dromedary Camels (Camelus dromedarius)

Christian A. Devaux / Ikram Omar Osman / Matthieu Million / Didier Raoult

Frontiers in Veterinary Science, Vol

A Possible Threat for Humans and Livestock in North Africa and the Near and Middle East?

2020 Volume 7

Abstract: The “One Health” concept recognizes that human health is connected to animal health and to the ecosystems. Coxiella burnetii–induced human Q fever is one of the most widespread neglected zoonosis. The main animal reservoirs responsible for C. burnetii ... ...

Abstract	The “One Health” concept recognizes that human health is connected to animal health and to the ecosystems. Coxiella burnetii–induced human Q fever is one of the most widespread neglected zoonosis. The main animal reservoirs responsible for C. burnetii transmission to humans are domesticated ruminants, primarily goats, sheep, and cattle. Although studies are still too sparse to draw definitive conclusions, the most recent C. burnetii serosurvey studies conducted in herds and farms in Africa, North Africa, Arabian Peninsula, and Asia highlighted that seroprevalence was strikingly higher in dromedary camels (Camelus dromedarius) than in other ruminants. The C. burnetii seroprevalence in camel herds can reach more than 60% in Egypt, Saudi Arabia, and Sudan, and 70 to 80% in Algeria and Chad, respectively. The highest seroprevalence was in female camels with a previous history of abortion. Moreover, C. burnetii infection was reported in ticks of the Hyalomma dromedarii and Hyalomma impeltatum species collected on camels. Even if dromedary camels represent <3% of the domesticated ruminants in the countries of the Mediterranean basin Southern coast, these animals play a major socioeconomic role for millions of people who live in the arid zones of Africa, Middle East, and Asia. In Chad and Somalia, camels account for about 7 and 21% of domesticated ruminants, respectively. To meet the growing consumers demand of camel meat and milk (>5 million tons/year of both raw and pasteurized milk according to the Food and Agriculture Organization) sustained by a rapid increase of population (growth rate: 2.26–3.76 per year in North Africa), dromedary camel breeding tends to increase from the Maghreb to the Arabic countries. Because of possible long-term persistence of C. burnetii in camel hump adipocytes, this pathogen could represent a threat for herds and breeding farms and ultimately for public health. Because this review highlights a hyperendemia of C. burnetii in dromedary camels, a proper screening of herds and ...
Keywords	Coxiella burnetii ; dromedary camel (Camelus dromedarius) ; zoonoses awareness ; epidemiology ; human—animal coexistence ; Veterinary medicine ; SF600-1100
Subject code	390
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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