International Center for Infectiology Research

Sainte-Foy-lès-Lyon, France

International Center for Infectiology Research

Sainte-Foy-lès-Lyon, France
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Hodille E.,International Center for Infectiology Research | Hodille E.,Ecole Normale Superieure de Lyon | Hodille E.,Institute des Agents Infectieux | Alekseeva L.,French National Institute for Agricultural Research | And 19 more authors.
Frontiers in Microbiology | Year: 2016

Maintenance of an intact epithelial barrier constitutes a pivotal defense mechanism against infections. Staphylococcus aureus is a versatile pathogen that produces multiple factors including exotoxins that promote tissue alterations. The aim of the present study is to investigate the cytopathic effect of staphylococcal exotoxins SEA, SEG, SEI, SElM, SElN and SElO on the cell cycle of various human cell lines. Among all tested exotoxins only SEIO inhibited the proliferation of a broad panel of human tumor cell lines in vitro. Evaluation of a LDH release and a DNA fragmentation of host cells exposed to SEIO revealed that the toxin does not induce necrosis or apoptosis. Analysis of the DNA content of tumor cells synchronized by serum starvation after exposure to SEIO showed G0/G1 cell cycle delay. The cell cycle modulating feature of SEIO was confirmed by the flow cytometry analysis of synchronized cells exposed to supernatants of isogenic S. aureus strains wherein only supernatant of the SElO producing strain induced G0/G1 phase delay. The results of yeast-two-hybrid analysis indicated that SEIO's potential partner is cullin-3, involved in the transition from G1 to S phase. In conclusion, we provide evidence that SEIO inhibits cell proliferation without inducing cell death, by delaying host cell entry into the G0/G1 phase of the cell cycle. We speculate that this unique cell cycle modulating feature allows SEIO producing bacteria to gain advantage by arresting the cell cycle of target cells as part of a broader invasive strategy. © 2016 Hodille, Alekseeva, Berkova, Serrier, Badiou, Gilquin, Brun, Vandenesch, Terman and Lina.


Horvat B.,International Center for Infectiology Research | Horvat B.,French Institute of Health and Medical Research | Horvat B.,French National Center for Scientific Research | Horvat B.,University of Lyon | And 3 more authors.
Current Opinion in Virology | Year: 2014

Progress in the identification of suitable animal models for human herpesvirus (HHV)-6A and HHV-6B infections has been slow. Recently, new models have been established, mainly for HHV-6A, which reproduce some pathological features seen in humans. Neuroinflammatory signs were observed in infected marmosets and CD46-transgenic mice; although viral replication was not prominent, persistence of viral DNA and specific immunologic responses were detected, suggesting an immune-mediated pathogenic mechanism. Pig-tailed macaques showed robust viral replication concomitant with acute-phase symptoms, and provided a model to study the effects of HHV-6A on AIDS progression. In humanized mice, viral replication was less evident, but infection led to T-cell alterations. Altogether, these recent developments have opened new perspectives for studying the pathogenic role of HHV-6A in humans. © 2014, Elsevier B.V. All rights reserved.


Baumert T.F.,University of Strasbourg | Baumert T.F.,Institut Universitaire de France | Schuster C.,University of Strasbourg | Cosset F.-L.,International Center for Infectiology Research | And 8 more authors.
Journal of Hepatology | Year: 2016

Following the discovery of the hepatitis C virus (HCV) more than 25 years ago the field has succeeded to develop methods that have changed the safety of blood products, understand the molecular virology, epidemiology and clinical disease of HCV, and identify specific targets for the development of direct-acting antivirals for HCV cure. Nevertheless, major clinical and scientific challenges remain: therapy is still only available to a fraction of infected patients worldwide and many patients remain undiagnosed and/or live in countries where therapy is unattainable. An urgently needed HCV vaccine to eradicate infection remains still elusive. Scientifically, major questions remain regarding the life cycle, pathogenesis and mechanisms of viral clearance and persistence. Addressing these challenges, this meeting report reviews key findings of the 22nd International Symposium on Hepatitis C Virus and Related Viruses in Strasbourg, France from October 9 to 13, 2015. © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Mathieu C.,International Center for Infectiology Research | Mathieu C.,French Institute of Health and Medical Research | Mathieu C.,French National Center for Scientific Research | Mathieu C.,University of Lyon | And 8 more authors.
Expert Review of Anti-Infective Therapy | Year: 2015

Hendra virus and Nipah virus are closely related, recently emerged zoonotic paramyxoviruses, belonging to the Henipavirus genus. Both viruses induce generalized vasculitis affecting particularly the respiratory tract and CNS. The exceptionally broad species tropism of Henipavirus, the high case fatality rate and person-to-person transmission associated with Nipah virus outbreaks emphasize the necessity of effective antiviral strategies for these intriguing threatening pathogens. Current therapeutic approaches, validated in animal models, target early steps in viral infection; they include the use of neutralizing virus-specific antibodies and blocking membrane fusion with peptides that bind the viral fusion protein. A better understanding of Henipavirus pathogenesis is critical for the further advancement of antiviral treatment, and we summarize here the recent progress in the field. © 2015 Informa UK, Ltd


Hammann P.,University of Strasbourg | Parmentier D.,University of Strasbourg | Cerciat M.,University of Strasbourg | Reimegard J.,Uppsala University | And 7 more authors.
Biochimie | Year: 2014

We have adapted a method to map cell surface proteins and to monitor the effect of specific regulatory RNAs on the surface composition of the bacteria. This method involves direct labeling of surface proteins of living bacteria using fluorescent dyes and a subsequent separation of the crude extract by 2D gel electrophoresis. The strategy yields a substantial enrichment in surface proteins over cytoplasmic proteins. We validated this method by monitoring the effect of the regulatory RNA MicA in Escherichia coli, which regulates the synthesis of several outer membrane proteins, and highlighted the role of Staphylococcus aureus RNAIII for the maintenance of cell wall integrity. © 2014 The Authors.


Nitzan M.,Hebrew University of Jerusalem | Fechter P.,University of Strasbourg | Peer A.,Hebrew University of Jerusalem | Altuvia Y.,Hebrew University of Jerusalem | And 9 more authors.
Nucleic Acids Research | Year: 2015

Cells adapt to environmental changes by efficiently adjusting gene expression programs. Staphylococcus aureus, an opportunistic pathogenic bacterium, switches between defensive and offensive modes in response to quorum sensing signal. We identified and studied the structural characteristics and dynamic properties of the core regulatory circuit governing this switch by deterministic and stochastic computational methods, as well as experimentally. This module, termed here Double Selector Switch (DSS), comprises the RNA regulator RNAIII and the transcription factor Rot, defining a double-layered switch involving both transcriptional and post-transcriptional regulations. It coordinates the inverse expression of two sets of target genes, immuno-modulators and exotoxins, expressed during the defensive and offensive modes, respectively. Our computational and experimental analyses show that the DSS guarantees fine-tuned coordination of the inverse expression of its two gene sets, tight regulation, and filtering of noisy signals. We also identified variants of this circuit in other bacterial systems, suggesting it is used as a molecular switch in various cellular contexts and offering its use as a template for an effective switching device in synthetic biology studies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.


Tawar R.G.,French Institute of Health and Medical Research | Tawar R.G.,University of Strasbourg | Colpitts C.C.,French Institute of Health and Medical Research | Colpitts C.C.,University of Strasbourg | And 17 more authors.
Hepatology | Year: 2015

Hepatitis C virus (HCV) causes persistent infection in the majority of infected individuals. The mechanisms of persistence and clearance are only partially understood. Antibodies (Abs) against host cell entry receptors have been shown to inhibit HCV infection in cell culture and animal models. In this study, we aimed to investigate whether anti-receptor Abs are induced during infection in humans in vivo and whether their presence is associated with outcome of infection. We established an enzyme-linked immunosorbant assay using a recombinant CD81-claudin-1 (CLDN1) fusion protein to detect and quantify Abs directed against extracellular epitopes of the HCV CD81-CLDN1 coreceptor complex. The presence of anti-receptor Abs was studied in serum of patients from a well-defined cohort of a single-source HCV outbreak of pregnant women and several control groups, including uninfected pregnant women, patients with chronic hepatitis B and D virus (HBV/HDV) infection, and healthy individuals. Virus-neutralizing activity of Abs was determined using recombinant cell culture-derived HCV (HCVcc). Our results demonstrate that HCV-infected patients have statistically significantly higher anti-CD81/CLDN1 Ab titers during the early phase of infection than controls. The titers were significantly higher in resolvers compared to persisters. Functional studies using immunoadsorption and HCV cell culture models demonstrate that HCV-neutralizing anti-receptor Abs are induced in the early phase of HCV infection, but not in control groups. Conclusion: The virus-neutralizing properties of these Abs suggest a role for control of viral infection in conjunction with antiviral responses. Characterization of these anti-receptor Abs opens new avenues to prevent and treat HCV infection. (Hepatology 2015;62:726-736). © 2015 by the American Association for the Study of Liver Diseases.


Benet T.,Edouard Herriot Hospital | Benet T.,University of Lyon | Benet T.,International Center for Infectiology Research | Sylla M.,Gabriel Toure Hospital | And 18 more authors.
PLoS ONE | Year: 2015

Background: There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali. Methods: A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression. Results: Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6-7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0-151.4), respiratory syn-cytial virus [RSV] (aOR = 7.4, 95% CI: 2.3-23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0-112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneu-mococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively). Conclusions In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumo-coccal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries. © 2015 Bénet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


PubMed | Center dInfectiologie Charles Merieux, Edouard Herriot Hospital, International Center for Infectiology Research and Gabriel Toure Hospital
Type: Journal Article | Journal: PloS one | Year: 2015

There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali.A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Tour University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression.Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6-7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0-151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3-23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0-112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively).In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.

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