Didier Raoult

Aix-Marseille Université, Marsiglia, Provence-Alpes-Côte d'Azur, France

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Publications (812)4286.35 Total impact

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    ABSTRACT: The emergence of colistin-resistant Klebsiella pneumoniae (CRKP) is a major public health concern worldwide. In this study, the prevalence and molecular basis of colistin resistance in CRKP isolated from healthy individuals and patients in Lao PDR, Thailand, Nigeria and France was investigated. Stool samples were screened by culture for the presence of colistin-resistant Klebsiella spp. Whole-genome sequence analysis was used to decipher the molecular mechanism of colistin resistance in a blaNDM-1-positive in vitro-selected CRKP mutant. PCR amplification and sequencing of the mgrB genetic environment was performed for all CRKP isolates as well as control colistin-susceptible K. pneumoniae (CSKP) isolates recovered from the same stools. A total of 869 stool samples were screened for colistin-resistant Klebsiella spp., yielding 32 CRKP and 2 colistin-resistant Klebsiella oxytoca. Comparative whole-genome sequence analysis revealed that an in vitro-selected CRKP mutant had an insertion sequence in its mgrB gene, as well as missense mutations in other selected clones. Of the 34 colistin-resistant Klebsiella spp. isolates, 14 (41.2%; 13 CRKP and 1 K. oxytoca) from the four countries also had various defects in their mgrB genes, but no such defects were found in the CSKP controls (P < 10−4). Few mutations were observed in pmrAB compared with mgrB among the CRKP isolates. The worldwide emergence of CRKP is a major public health concern. Detection and surveillance of such strains are warranted to prevent an uncontrollable pandemic. Inactivation of the PhoP/PhoQ regulator gene mgrB is associated with ≥40% of colistin resistance among the CRKP isolates observed in this study.
    International Journal of Antimicrobial Agents. 01/2014;
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    ABSTRACT: In Africa, there are several problems with the specific identification of bacteria. Recently, MALDI-TOF mass spectrometry has become a powerful tool for the routine microbial identification in many clinical laboratories. This study was conducted using feces from 347 individuals (162 with diarrhea and 185 without diarrhea) sampled in health centers in Dakar, Senegal. Feces were transported from Dakar to Marseille, France, where they were cultured using different culture conditions. The isolated colonies were identified using MALDI-TOF. If a colony was unidentified, 16S rRNA sequencing was performed. Overall, 2,753 isolates were tested, allowing for the identification of 189 bacteria from 5 phyla, including 2 previously unknown species, 11 species not previously reported in the human gut, 10 species not previously reported in humans, and 3 fungi. 2,718 bacterial isolates (98.8%) out of 2,750 yielded an accurate identification using mass spectrometry, as did the 3 Candida albicans isolates. Thirty-two bacterial isolates not identified by MALDI-TOF (1.2%) were identified by sequencing, allowing for the identification of 2 new species. The number of bacterial species per fecal sample was significantly higher among patients without diarrhea (8.6±3) than in those with diarrhea (7.3±3.4; P = 0.0003). A modification of the gut microbiota was observed between the two groups. In individuals with diarrhea, major commensal bacterial species such as E. coli were significantly decreased (85% versus 64%), as were several Enterococcus spp. (E. faecium and E. casseliflavus) and anaerobes, such as Bacteroides spp. (B. uniformis and B. vulgatus) and Clostridium spp. (C. bifermentans, C. orbiscindens, C. perfringens, and C. symbosium). Conversely, several Bacillus spp. (B. licheniformis, B. mojavensis, and B. pumilus) were significantly more frequent among patients with diarrhea. MALDI-TOF is a potentially powerful tool for routine bacterial identification in Africa, allowing for a quick identification of bacterial species.
    PLoS ONE 01/2014; 9(5):e87419. · 3.53 Impact Factor
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    ABSTRACT: Many human viral infections have a zoonotic, i.e., wild or domestic animal, origin. Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and replicate in its new human host, human-to-human transmissions may occur, possibly resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus, predicting emerging zoonotic infections is an important challenge for public health officials in the coming decades. The recent development of viral metagenomics, i.e., the characterization of the complete viral diversity isolated from an organism or an environment using high-throughput sequencing technologies, is promising for the surveillance of such diseases and can be accomplished by analyzing the viromes of selected animals and arthropods that are closely in contact with humans. In this review, we summarize our current knowledge of viral diversity within such animals (in particular blood-feeding arthropods, wildlife and domestic animals) using metagenomics and present its possible future application for the surveillance of zoonotic and arboviral diseases.
    International Journal of Molecular Sciences 01/2014; 15(6):10377-10397. · 2.46 Impact Factor
  • Emmanouil Angelakis, Didier Raoult
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    ABSTRACT: Recently, there has been a steady increase in the number of recognized pathogenic microorganisms, specifically bacteria. The development of genetic technologies, MALDI-TOF mass spectrometry and new culturing techniques has significantly widened the repertoire of known microorganisms and therefore pathogenic microorganisms. The repertoire of infectious agents has been studied in various environments including water, soil, pets, livestock, wildlife and arthropods. Using different methods, many known pathogens can be identified in these samples; therefore, the impact of emergent pathogens on humans can be examined and novel pathogens can be identified. In this special issue, we discuss the identification of emerging pathogens in the environment and animals.
    Microbial Pathogenesis 01/2014; · 1.97 Impact Factor
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    ABSTRACT: Q fever endocarditis, a severe complication of Q fever, is associated with a defective immune response, the mechanisms of which are poorly understood. We hypothesized that Q fever immune deficiency is related to altered distribution and activation of circulating monocyte subsets. Monocyte subsets were analyzed by flow cytometry in peripheral blood mononuclear cells from patients with Q fever endocarditis and controls. The proportion of classical monocytes (CD14+CD16- monocytes) was similar in patients and controls. In contrast, the patients with Q fever endocarditis exhibited a decrease in the non-classical and intermediate subsets of monocytes (CD16+ monocytes). The altered distribution of monocyte subsets in Q fever endocarditis was associated with changes in their activation profile. Indeed, the expression of HLA-DR, a canonical activation molecule, and PD-1, a co-inhibitory molecule, was increased in intermediate monocytes. This profile was not restricted to CD16+ monocytes because CD4+ T cells also overexpressed PD-1. The mechanism leading to the overexpression of PD-1 did not require the LPS from C. burnetii but involved interleukin-10, an immunosuppressive cytokine. Indeed, the incubation of control monocytes with interleukin-10 led to a higher expression of PD-1 and neutralizing interleukin-10 prevented C. burnetii-stimulated PD-1 expression. Taken together, these results show that the immune suppression of Q fever endocarditis involves a cross-talk between monocytes and CD4+ T cells expressing PD-1. The expression of PD-1 may be useful to assess chronic immune alterations in Q fever endocarditis.
    PLoS ONE 01/2014; 9(9):e107533. · 3.53 Impact Factor
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    ABSTRACT: Pericarditis is a common human disease defined by inflammation of the pericardium. Currently, 40% to 85% of pericarditis cases have no identified etiology. Most of these cases are thought to be caused by an infection of undetected, unsuspected or unknown viruses. In this work, we used a culture- and sequence-independent approach to investigate the viral DNA communities present in human pericardial fluids. Seven viral metagenomes were generated from the pericardial fluid of patients affected by pericarditis of unknown etiology and one metagenome was generated from the pericardial fluid of a sudden infant death case. As a positive control we generated one metagenome from the pericardial fluid of a patient affected by pericarditis caused by herpesvirus type 3. Furthermore, we used as negative controls a total of 6 pericardial fluids from 6 different individuals affected by pericarditis of non-infectious origin: 5 of them were sequenced as a unique pool and the remaining one was sequenced separately. The results showed a significant presence of torque teno viruses especially in one patient, while herpesviruses and papillomaviruses were present in the positive control. Co-infections by different genotypes of the same viral type (torque teno viruses) or different viruses (herpesviruses and papillomaviruses) were observed. Sequences related to bacteriophages infecting Staphylococcus, Enterobacteria, Streptococcus, Burkholderia and Pseudomonas were also detected in three patients. This study detected torque teno viruses and papillomaviruses, for the first time, in human pericardial fluids.
    PLoS ONE 01/2014; 9(4):e93367. · 3.53 Impact Factor
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    ABSTRACT: We announce the draft genome sequence of Mycobacterium cosmeticum strain DSM 44829, a nontuberculous species responsible for opportunistic infection. The genome described here is composed of 6,462,090 bp, with a G+C content of 68.24%. It contains 6,281 protein-coding genes and 75 predicted RNA genes.
    Genome announcements. 01/2014; 2(2).
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    ABSTRACT: Proliferation of Demodex mites is associated with rosacea. Furthermore, Demodex-associated bacteria were suggested to play a role in the pathogenesis of rosacea. We decided to analyze Demodex microbiota. Mites were collected by standardized skin surface biopsies from patients with erythematotelangiectatic, papulopustular rosacea or from control subjects. The microbiota from each mite was characterized by 16S rRNA clone library approach. The 16S rRNA clone library consisted of 367 clones obtained from 73 extracts originating from 5 samples per study group (ETR, PPR or healthy subjects). A total of 86 species were identified with 36 as Demodex-specific microbiota. In the papulopustular group, proportions of Proteobacteria and Firmicutes increased whereas proportion of Actinobacteria decreased. Here, we report preliminary results on the microbiota of Demodex mites based on a molecular approach showing an unexpected diversity. Differences according to the host status need to be confirmed but open new perspectives for diagnostic of rosacea.
    Microbial Pathogenesis 01/2014; · 1.97 Impact Factor
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    ABSTRACT: We report the draft genome sequence of Mycobacterium vulneris DSM 45247(T) strain, an emerging, opportunistic pathogen of the Mycobacterium avium complex. The genome described here is composed of 6,981,439 bp (with a G+C content of 67.14%) and has 6,653 protein-coding genes and 84 predicted RNA genes.
    Genome announcements. 01/2014; 2(3).
  • Journal of Infection. 01/2014;
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    ABSTRACT: Expressing mspA porin gene from Mycobacterium smegmatis in Mycobacterium tuberculosis attenuated this pathogen. Intracellular growth of the transformants into free-living amoeba and murine and human macrophages decreased. Furthermore, transformants decreased the microbicidal program of human monocyte-derived macrophages. BALB/c mice inoculated with transformants exhibited higher weights, lower histological lesions and lower M. tuberculosis inoculum in the liver, spleen and lungs than control mice challenged with wild-type M. tuberculosis. Preliminary evaluation indicated that mice inoculated with this transformant showed higher weights and lower numbers of lung nodules and tissular mycobacteria than control mice when challenged with wild-type M. tuberculosis. Similar to the paradoxical “unbirthday” gift coined by Lewis Carroll in Alice’s Adventures in Wonderland, adding mspA gene reduced the virulence of M. tuberculosis and yielded a protective effect. Lost of non-virulence genes is a mechanism for virulence in mycobacteria. Engineering non-virulence genes in M. tuberculosis may yield strains with decreased virulence and increased immunogenicity.
    Microbial Pathogenesis 01/2014; · 1.97 Impact Factor
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    ABSTRACT: We report the draft genome sequence of Mycobacterium asiaticum strain DSM 44297, a tropical mycobacterium seldom responsible for human infection. The genome of M. asiaticum has a size of 5,935,986 bp, with a 66.03% G+C content, encoding 5,591 proteins and 81 RNAs.
    Genome announcements. 01/2014; 2(2).
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    ABSTRACT: We report the draft genome sequence of Mycobacterium mageritense strain DSM 44476(T) (CIP 104973), a nontuberculosis species responsible for various infections. The genome described here is composed of 7,966,608 bp, with a G+C content of 66.95%, and contains 7,675 protein-coding genes and 120 predicted RNA genes.
    Genome announcements. 01/2014; 2(2).
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    ABSTRACT: The consumption of insects by apes has previously been reported based on direct observations and/or trail signs in feces. However, DNA-based diet analyses may have the potential to reveal trophic links for these wild species. Herein, we analyzed the insect-diet diversity of 9 feces obtained from three species of African great apes, gorilla (Gorilla gorilla gorilla), chimpanzee (Pan troglodytes) and bonobo (Pan paniscus), using two mitochondrial amplifications for arthropods. A total of 1056 clones were sequenced for Cyt-b and COI gene libraries, which contained 50 and 56 operational taxonomic units (OTUs), respectively. BLAST research revealed that the OTUs belonged to 32 families from 5 orders (Diptera, Isoptera, Lepidoptera, Coleoptera, and Orthoptera). While ants were not detected by this method, the consumption of flies, beetles, moths, mosquitoes and termites was evident in these samples. Our findings indicate that molecular techniques can be used to analyze insect food items in wild animals.
    Scientific Reports 01/2014; 4:4478. · 5.08 Impact Factor
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    ABSTRACT: We announce the draft genome sequence of Mycobacterium austroafricanum DSM 44191(T) (= E9789-SA12441(T)), a non-tuberculosis species responsible for opportunistic infection. The genome described here has a size of 6,772,357 bp with a G+C content of 66.79% and contains 6,419 protein-coding genes and 112 RNA genes.
    Genome announcements. 01/2014; 2(2).
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    ABSTRACT: Recently, tissue-based methods for proteomic analysis have been used in clinical research and appear reliable for digestive, brain, lymphomatous, and lung cancers classification. However simple, tissue-based methods that couple signal analysis to tissue imaging are time consuming. To assess the reliability of a method involving rapid tissue preparation and analysis to discriminate cancerous from non-cancerous tissues, we tested 141 lung cancer/non-tumor pairs and 8 unique lung cancer samples among the stored frozen samples of 138 patients operated on during 2012. Samples were crushed in water, and 1.5 µl was spotted onto a steel target for analysis with the Microflex LT analyzer (Bruker Daltonics). Spectra were analyzed using ClinProTools software. A set of samples was used to generate a random classification model on the basis of a list of discriminant peaks sorted with the k-nearest neighbor genetic algorithm. The rest of the samples (n = 43 cancerous and n = 41 non-tumoral) was used to verify the classification capability and calculate the diagnostic performance indices relative to the histological diagnosis. The analysis found 53 m/z valid peaks, 40 of which were significantly different between cancerous and non-tumoral samples. The selected genetic algorithm model identified 20 potential peaks from the training set and had 98.81% recognition capability and 89.17% positive predictive value. In the blinded set, this method accurately discriminated the two classes with a sensitivity of 86.7% and a specificity of 95.1% for the cancer tissues and a sensitivity of 87.8% and a specificity of 95.3% for the non-tumor tissues. The second model generated to discriminate primary lung cancer from metastases was of lower quality. The reliability of MALDI-ToF analysis coupled with a very simple lung preparation procedure appears promising and should be tested in the operating room on fresh samples coupled with the pathological examination.
    PLoS ONE 01/2014; 9(5):e97511. · 3.53 Impact Factor
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    ABSTRACT: Rickettsia tamurae is a member of the spotted fever group rickettsiae, which was reported in 2011 to cause human infections in Japan. We report the draft genome sequence of R. tamurae strain AT-1(T), isolated from Amblyomma testudinarium ticks.
    Genome announcements. 01/2014; 2(5).
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    ABSTRACT: ldemania massiliensis strain AP2T sp. nov. is the type strain of H. massiliensis sp. nov., a new species within the genus Holdemania. This strain, whose genome is described here, was isolated from the fecal flora of a 21-year-old French Caucasian female suffering from severe restrictive anorexia nervosa. H. massiliensis is a Gram-positive, anaerobic bacillus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 3,795,625 bp-long genome (one chromosome but no plasmid) contains 3,461 protein-coding and 49 RNA genes, including 3 rRNA genes.
    Standards in Genomic Sciences 12/2013; · 3.17 Impact Factor
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    ABSTRACT: Abstract Ticks, belonging to the soft ticks species Ornithodorus sonrai, have been collected from six sites in Senegal and were tested for the presence of Bartonella spp. Initial screening by PCR revealed the presence of these bacteria in ticks from two villages, Soulkhou Thissé (5/8, 62.5%) and Maka Gouye (1/24, 4.2%). Three bacterial strains were isolated from live ticks, and the genetic characterization of these strains suggests that they belong to two previously unknown species. The pathogenicity of these two new species of Bartonella is not yet known. The new isolates described here are the first strains of Bartonella spp. from soft ticks and the first isolates from any arthropod species in Africa.
    Vector borne and zoonotic diseases (Larchmont, N.Y.) 12/2013; · 2.61 Impact Factor
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    ABSTRACT: Phocaeicola abscessus strain 7401987(T) is the sole member of the genus Phocaeicola. This bacterium is Gram-negative, non-spore-forming, coccoid to rod-shaped and motile by lophotrichous flagella. It was isolated from a human brain abscess sample. In this work, we describe a set of features of this organism, together with the complete genome sequence and annotation. The 2,530,616 bp long genome contains 2,090 protein-coding genes and 54 RNA genes, including 4 rRNA operons.
    Standards in Genomic Sciences 12/2013; 9(2):351-8. · 3.17 Impact Factor

Publication Stats

14k Citations
4,286.35 Total Impact Points


  • 2002–2014
    • Aix-Marseille Université
      • • Faculté de Médecine
      • • Unité de Recherche sur les maladies Infectieuses et Tropicales Emergentes (UM 63 UMR_S 1095 UMR 7278 URMITE)
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
    • University of Alberta
      • Department of Medicine
      Edmonton, Alberta, Canada
  • 1999–2013
    • French National Centre for Scientific Research
      • Laboratoire Information Génomique et Structurale (IGS)
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • University of Science and Technology Houari Boumediene
      Le Retour de la Chasse, Alger, Algeria
    • Soroka Medical Center
      • Soroka Medical Center
      Be'er Sheva`, Southern District, Israel
    • Umeå University
      • Department of Molecular Biology
      Umeå, Västerbotten, Sweden
    • University of Udine
      Udine, Friuli Venezia Giulia, Italy
    • DRK Manniske Krankenhaus
      Frankenhausen, Thuringia, Germany
  • 2011–2012
    • Slovak Academy of Sciences
      • Institute of Virology
      Presburg, Bratislavský, Slovakia
    • Hôpital Européen, Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2008–2012
    • Istituto Zooprofilattico Sperimentale della Sardegna
      Sassari, Sardinia, Italy
    • University of Madras
      Chennai, Tamil Nādu, India
    • Duke University Medical Center
      Durham, North Carolina, United States
  • 2009–2011
    • Institut de Recherche sur les Phénomènes Hors Equilibre
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • New York State Department of Health
      New York City, New York, United States
    • National Institutes of Health
      • National Center for Biotechnology Information
      Bethesda, MD, United States
    • University of Lausanne
      • Department of Fundamental Microbiology (DMF)
      Lausanne, VD, Switzerland
  • 2010
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
    • Hôpitaux Universitaires de Genève
      Genève, Geneva, Switzerland
    • Indira Gandhi Medical College
      Simla, Himachal Pradesh, India
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
    • Wageningen University
      Wageningen, Gelderland, Netherlands
  • 2009–2010
    • Institute of Research for Development
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2006–2010
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
    • Research Institute of Epidemiology and Microbiology n.a. N. F. Gamalei, Russian Academy of Medical Sciences
      Moskva, Moscow, Russia
    • Hospital Universitario de Canarias
      San Cristóbal de La Laguna, Canary Islands, Spain
    • Centre Hospitalier Régional d'Oran
      Wahrān, Oran, Algeria
    • Niigata City General Hospital
      Niahi-niigata, Niigata, Japan
  • 2003–2009
    • Assistance Publique Hôpitaux de Marseille
      • Laboratoire de bactériologie
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Ross University
      Basse Terre Town, Saint George Basseterre, Saint Kitts and Nevis
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Dalhousie University
      Halifax, Nova Scotia, Canada
    • Armed Forces Research Institute of Medical Sciences
      Krung Thep, Bangkok, Thailand
  • 2004–2006
    • Oslo University Hospital
      • Department of Infectious Diseases
      Kristiania (historical), Oslo County, Norway
    • Aalborg University Hospital
      • Department of Infectious Diseases
      Aalborg, Region North Jutland, Denmark
    • Aglaia Kyriakou Children's Hospital
      Athínai, Attica, Greece
  • 2005
    • Ross University, School of Medicine
      Ross, Ohio, United States
    • University Hospital of Lausanne
      Lausanne, Vaud, Switzerland
  • 2002–2003
    • Yamaguchi University
      • Faculty of Agriculture
      Yamaguchi-shi, Yamaguchi-ken, Japan