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Dive into the research topics where Eric Valade is active.

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Featured researches published by Eric Valade.


PLOS Genetics | 2013

The condition-dependent transcriptional landscape of Burkholderia pseudomallei.

Wen Fong Ooi; Catherine Ong; Tannistha Nandi; Jason F. Kreisberg; Hui Hoon Chua; Guangwen Sun; Yahua Chen; Claudia Mueller; Laura Conejero; Majid Eshaghi; Roy Moh Lik Ang; Jianhua Liu; Bruno W. S. Sobral; Sunee Korbsrisate; Yunn Hwen Gan; Richard W. Titball; Gregory J. Bancroft; Eric Valade; Patrick Tan

Burkholderia pseudomallei (Bp), the causative agent of the often-deadly infectious disease melioidosis, contains one of the largest prokaryotic genomes sequenced to date, at 7.2 Mb with two large circular chromosomes (1 and 2). To comprehensively delineate the Bp transcriptome, we integrated whole-genome tiling array expression data of Bp exposed to >80 diverse physical, chemical, and biological conditions. Our results provide direct experimental support for the strand-specific expression of 5,467 Sanger protein-coding genes, 1,041 operons, and 766 non-coding RNAs. A large proportion of these transcripts displayed condition-dependent expression, consistent with them playing functional roles. The two Bp chromosomes exhibited dramatically different transcriptional landscapes — Chr 1 genes were highly and constitutively expressed, while Chr 2 genes exhibited mosaic expression where distinct subsets were expressed in a strongly condition-dependent manner. We identified dozens of cis-regulatory motifs associated with specific condition-dependent expression programs, and used the condition compendium to elucidate key biological processes associated with two complex pathogen phenotypes — quorum sensing and in vivo infection. Our results demonstrate the utility of a Bp condition-compendium as a community resource for biological discovery. Moreover, the observation that significant portions of the Bp virulence machinery can be activated by specific in vitro cues provides insights into Bps capacity as an “accidental pathogen”, where genetic pathways used by the bacterium to survive in environmental niches may have also facilitated its ability to colonize human hosts.


PLOS ONE | 2011

Involvement of the efflux pumps in chloramphenicol selected strains of Burkholderia thailandensis: proteomic and mechanistic evidence.

Fabrice V. Biot; Eric Valade; Eric Garnotel; Jacqueline Chevalier; Claude Villard; François M. Thibault; Dominique R. Vidal; Jean-Marie Pagès

Burkholderia is a bacterial genus comprising several pathogenic species, including two species highly pathogenic for humans, B. pseudomallei and B. mallei. B. thailandensis is a weakly pathogenic species closely related to both B. pseudomallei and B. mallei. It is used as a study model. These bacteria are able to exhibit multiple resistance mechanisms towards various families of antibiotics. By sequentially plating B. thailandensis wild type strains on chloramphenicol we obtained several resistant variants. This chloramphenicol-induced resistance was associated with resistance against structurally unrelated antibiotics including quinolones and tetracyclines. We functionally and proteomically demonstrate that this multidrug resistance phenotype, identified in chloramphenicol-resistant variants, is associated with the overexpression of two different efflux pumps. These efflux pumps are able to expel antibiotics from several families, including chloramphenicol, quinolones, tetracyclines, trimethoprim and some β-lactams, and present a partial susceptibility to efflux pump inhibitors. It is thus possible that Burkholderia species can develop such adaptive resistance mechanisms in response to antibiotic pressure resulting in emergence of multidrug resistant strains. Antibiotics known to easily induce overexpression of these efflux pumps should be used with discernment in the treatment of Burkholderia infections.


Journal of Antimicrobial Chemotherapy | 2010

Phenotypic and genetic characterization of macrolide resistance in Francisella tularensis subsp. holarctica biovar I

Brieuc Gestin; Eric Valade; François M. Thibault; Dominique Schneider; Max Maurin

OBJECTIVES Francisella tularensis subsp. holarctica strains are classified as biovars I and II, which are susceptible and naturally resistant to the macrolide erythromycin, respectively. The present study was aimed at both selecting biovar I strains with increased levels of erythromycin resistance and characterizing the underlying genetic mechanisms. METHODS Serial cultures in the presence of increasingly high erythromycin concentrations were performed to select independent high- and intermediate-level erythromycin-resistant mutants from each of three different biovar I strains. The mutants were characterized for cross-resistance to several antibiotics, presence of mutations in the genes encoding the 23S rRNA and the L4 and L22 ribosomal proteins, and overexpression of efflux pumps. RESULTS Mutants displayed cross-resistance to all macrolide compounds tested but not to other classes of antibiotics. We found mutations in domain V of the 23S rRNA gene (G2057A, A2058G, A2058T and C2611T) and in the gene encoding L22, leading to either the G91D substitution or the M82K83R84 deletion. Analysis of mutants with intermediate resistance levels obtained over the course of the selection process revealed both a positive correlation between the number of mutated ribosomal operons and the resistance level, and an additional resistance mechanism in the early steps of selection. CONCLUSIONS We showed that high-level resistance to macrolides can be easily obtained in vitro in F. tularensis subsp. holarctica biovar I strains, thereby suggesting that in vivo selection for resistance may explain reported failures of antibiotic treatment. Ketolides were the most effective macrolides tested, which may limit the risk of selection for resistance.


Journal of Antimicrobial Chemotherapy | 2008

Susceptibility of 71 French isolates of Francisella tularensis subsp. holarctica to eight antibiotics and accuracy of the Etest® method

Eric Valade; Josée Vaissaire; Audrey Mérens; Eric Hernandez; Chantal Gros; Claudine Le Doujet; Jean-Charles Paucod; François M. Thibault; Benoît Durand; Martine Lapalus; Isabelle Dupuis; Arnaud Caclard; Dominique R. Vidal; Jean-Didier Cavallo

1. Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? Clin Infect Dis 2002; 34: 634–40. 2. Pillar CM, Aranza MK, Shah D et al. In vitro activity profile of ceftobiprole, an anti-MRSA cephalosporin, against recent Gram-positive and Gram-negative isolates of European origin. J Antimicrob Chemother 2008; 61: 595–602. 3. Queenan AM, Shang W, Kania M et al. Interactions of ceftobiprole with b-lactamases from molecular classes A to D. Antimicrob Agents Chemother 2007; 51: 3089–95. 4. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Seventeenth Informational Supplement M100-S17. CLSI, Wayne, PA, USA, 2007. 5. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically— Seventh Edition: Approved Standard M7-A7. CLSI, Wayne, PA, USA, 2006. 6. Hebeisen P, Heinze-Krauss I, Angehrn P et al. In vitro and in vivo properties of Ro 63–9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci. Antimicrob Agents Chemother 2001; 45: 825–36.


PLOS ONE | 2013

Interplay between three RND efflux pumps in doxycycline-selected strains of Burkholderia thailandensis.

Fabrice V. Biot; Mélanie Monique Lopez; Thomas Poyot; Fabienne Neulat-Ripoll; Sabrina Lignon; Arnaud Caclard; François M. Thibault; Andre Peinnequin; Jean-Marie Pagès; Eric Valade

Background Efflux systems are involved in multidrug resistance in most Gram-negative non-fermentative bacteria. We have chosen Burkholderia thailandensis to dissect the development of multidrug resistance phenotypes under antibiotic pressure. Methodology/Principal Findings We used doxycycline selection to obtain several resistant B. thailandensis variants. The minimal inhibitory concentrations of a large panel of structurally unrelated antibiotics were determined ± the efflux pump inhibitor phenylalanine-arginine ß-naphthylamide (PAßN). Membrane proteins were identified by proteomic method and the expressions of major efflux pumps in the doxycycline selected variants were compared to those of the parental strains by a quantitative RT-PCR analysis. Doxycycline selected variants showed a multidrug resistance in two major levels corresponding to the overproduction of two efflux pumps depending on its concentration: AmrAB-OprA and BpeEF-OprC. The study of two mutants, each lacking one of these pumps, indicated that a third pump, BpeAB-OprB, could substitute for the defective pump. Surprisingly, we observed antagonistic effects between PAßN and aminoglycosides or some ß-lactams. PAßN induced the overexpression of AmrAB-OprA and BpeAB-OprB pump genes, generating this unexpected effect. Conclusions/Significance These results may account for the weak activity of PAßN in some Gram-negative species. We clearly demonstrated two antagonistic effects of this molecule on bacterial cells: the blocking of antibiotic efflux and an increase in efflux pump gene expression. Thus, doxycycline is a very efficient RND efflux pump inducer and PAßN may promote the production of some efflux pumps. These results should be taken into account when considering antibiotic treatments and in future studies on efflux pump inhibitors.


Methods of Molecular Biology | 2014

Galleria mellonella as an Infection Model for Select Agents

Nicolas Sprynski; Eric Valade; Fabienne Neulat-Ripoll

The use of animal models is a key step to better understand bacterial virulence factors and their roles in host/pathogen interactions. To avoid the ethical and cost problems of mammalian models in bacterial virulence research, several insect models have been developed. One of these models, the larvae of the greater wax moth Galleria mellonella, has been shown to be relevant for several fungal and bacterial mammalian pathogens. Here, we describe the use G. mellonella to study virulence of the highly virulent facultative intracellular bacterial pathogens: Brucella suis, Brucella melitensis, Francisella tularensis, Burkholderia mallei, and Burkholderia pseudomallei.


Emerging Infectious Diseases | 2016

Ebola Virus RNA Stability in Human Blood and Urine in West Africa's Environmental Conditions.

Frédéric Janvier; Déborah Delaune; Thomas Poyot; Eric Valade; Audrey Mérens; Pierre E. Rollin; Vincent Foissaud

We evaluated RNA stability of Ebola virus in EDTA blood and urine samples collected from infected patients and stored in West Africa’s environmental conditions. In blood, RNA was stable for at least 18 days when initial cycle threshold values were <30, but in urine, RNA degradation occurred more quickly.


Emerging Infectious Diseases | 2017

Occupational Exposures to Ebola Virus in Ebola Treatment Center, Conakry, Guinea

Hélène Savini; Frédéric Janvier; Ludovic Karkowski; M. Billhot; Marc Aletti; Julien Bordes; Fassou Koulibaly; Pierre-Yves Cordier; J.-M. Cournac; Nancy Maugey; Nicolas Gagnon; Jean Cotte; Audrey Cambon; Christine Mac Nab; Sophie Moroge; Claire Rousseau; Vincent Foissaud; Thierry De Greslan; H. Granier; Gilles Cellarier; Eric Valade; Philippe Kraemer; Philippe Alla; Audrey Mérens; Emmanuel Sagui; Thierry Carmoi; Christophe Rapp

We report 77 cases of occupational exposures for 57 healthcare workers at the Ebola Treatment Center in Conakry, Guinea, during the Ebola virus disease outbreak in 2014−2015. Despite the high incidence of 3.5 occupational exposures/healthcare worker/year, only 18% of workers were at high risk for transmission, and no infections occurred.


Tropical Medicine and Infectious Disease | 2018

Melioidosis in the Western Indian Ocean and the Importance of Improving Diagnosis, Surveillance, and Molecular Typing

Andriniaina Rakotondrasoa; Mohammad Iqbal Issack; Benoit Garin; Fabrice V. Biot; Eric Valade; Pierre Wattiau; Nicolas Allou; Olivier Belmonte; Jastin Bibi; Erin P. Price; Jean-Marc Collard

Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an infectious disease of humans or animals, and the specific environmental conditions that are present in western Indian Ocean islands are particularly suitable for the establishment/survival of B. pseudomallei. Indeed, an increasing number of new cases have been reported in this region (Madagascar, Mauritius, Réunion (France), and Seychelles, except Comoros and Mayotte (France)), and are described in this review. Our review clearly points out that further studies are needed in order to investigate the real incidence and burden of melioidosis in the western Indian Ocean and especially Madagascar, since it is likely to be higher than currently reported. Thus, research and surveillance priorities were recommended (i) to improve awareness of melioidosis in the population and among clinicians; (ii) to improve diagnostics, in order to provide rapid and effective treatment; (iii) to implement a surveillance and reporting system in the western Indian Ocean; and (iv) to investigate the presence of B. pseudomallei in environmental samples, since we have demonstrated its presence in soil samples originating from the yard of a Madagascan case.


Emerging Infectious Diseases | 2016

Melioidosis in Travelers Returning from Vietnam to France.

Jérôme Gauthier; Patrick Gérôme; Maryline Defez; Fabienne Neulat-Ripoll; Barbara Foucher; Thierry Vitry; L. Crevon; Eric Valade; François M. Thibault; Fabrice V. Biot

To the Editor: Melioidosis, a potentially fatal infectious disease, occurs predominantly across much of Asia and in northern Australia because of the soil and water bacterium Burkholderia pseudomallei (1). We report 2 related cases of suppurative cervical lymphadenitis, an unusual adult presentation of melioidosis, in 2 men who returned to France from Vietnam on the same trip (2).

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Audrey Mérens

Pierre-and-Marie-Curie University

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Arnaud Caclard

Aix-Marseille University

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Hervé Delacour

École Normale Supérieure

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