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September 2014 - present
January 2009 - March 2014
January 2006 - December 2009
Publications
Publications (84)
Carbapenemase-producing Enterobacterales (CPE) have been identified by the World Health Organization as global priority pathogens. The dissemination of these bacteria and outbreaks within healthcare facilities are of serious concern. This study investigated the transmission patterns and genetic characteristics of CPE isolated in New Caledonia from...
Site-specific endonucleases that exclusively cut single-stranded DNA have hitherto never been described and constitute a barrier to the development of ssDNA-based technologies. Here, we identify and characterize one such novel family of widely distributed site-specific single-stranded nucleases (Ssn) exhibiting unique ssDNA cleavage properties. Thi...
Bacteria employ diverse mechanisms to manage toxic copper in their environments, and these evolutionary strategies can be divided into two main categories: accumulation and rationalization of metabolic pathways. The strategies employed depend on the bacteria's lifestyle and environmental context, optimizing the metabolic cost-benefit ratio. Environ...
Background
Leptospirosis is a complex zoonotic disease mostly caused by a group of eight pathogenic species (L. interrogans, L. borgpetersenii, L. kirschneri, L. mayottensis, L. noguchii, L. santarosai, L. weilii, L. alexanderi), with a wide spectrum of animal reservoirs and patient outcomes. Leptospira interrogans is considered as the leading caus...
A polyphasic taxonomic approach, incorporating analysis of phenotypic features, cellular fatty acid profiles, 16S rRNA gene sequences, and determination of average nucleotide identity (ANI) plus digital DNA–DNA hybridization (dDDH), was applied to characterize an anaerobic bacterial strain designated KD22T isolated from human feces. 16S rRNA gene-b...
Different environments exert selective pressures on bacterial populations, favoring individuals with particular genetic traits that are well-suited for survival in those conditions. Evolutionary mechanisms such as natural selection have, therefore, shaped bacterial populations over time selecting, in a stepwise manner, the fittest bacteria that gav...
Strain KD21T, isolated from the fecal sample of a healthy female volunteer, is a strictly anaerobic, non-motile, Gram-staining-positive, saccharolytic small rod, that does not produce spores. Strain KD21T was able to grow in the range of temperature 28-37°C (optimum, 37 °C), pH 6.0-8.0 (optimum, pH 7.0), and with 0-5.0 g/L NaCl (optimum, 0 g/L NaCl...
Gamma irradiation of food products can provide an effective means of eliminating bacterial pathogens such as enterohemorrhagic Escherichia coli (EHEC) O157:H7, a significant foodborne pathogen that can cause severe disease due to the production of Stx. To decipher the mechanisms of adaptive resistance of the O157:H7 strain EDL933, we evolved clones...
Leptospira bacteria comprise numerous species, several of which cause serious disease to a broad range of hosts including humans. These spirochetes exhibit large intraspecific variation, resulting in complex tabulations of serogroups/serovars that crisscross the species classification. Serovar identity, linked to biological/clinical phenotypes, dep...
Glycosylated NPs, including liposomes, are known to target various receptors involved in cellular carbohydrate transport, of which the mannoside binding receptors are attracting particular attention for their expression on various immune cells, cancers, and cells involved in maintaining central nervous system (CNS) integrity. As part of our interes...
Rod-shaped bacteria typically elongate and divide by transverse fission. However, several bacterial species can form rod-shaped cells that divide longitudinally. Here, we study the evolution of cell shape and division mode within the family Neisseriaceae, which includes Gram-negative coccoid and rod-shaped species. In particular, bacteria of the ge...
Enterohemorragic Escherichia coli (EHEC) O157:H7 is a foodborne pathogen producing shiga toxins (Stx1 and Stx2), can cause hemorrhagic diarrhea, and life-threatening infections. O157:H7 strain EDL933 carries prophages CP-933V and BP-933W that encode shiga toxin genes ( stx1 and stx2 respectively). The aim of this work was to investigate the mechani...
The development of simple and highly efficient strategies for genetic modifications is essential for postgenetic studies aimed at characterizing gene functions for various applications. We sought to develop a reliable system for Neisseria species that allows for both unmarked and accumulation of multiple genetic modifications in a single strain. In...
Background
Although Southeast Asia is one of the most leptospirosis afflicted regions, little is known about the diversity and molecular epidemiology of the causative agents of this widespread and emerging zoonotic disease.
Methodology/Principal findings
We used whole genome sequencing to examine genetic variation in 75 Leptospira strains isolated...
In spite of the staggering number of bacteria that live associated with animals, the growth mode of only a few symbionts has been studied so far. Here, we focused on multicellular longitudinally dividing (MuLDi) Neisseriaceae occurring in the oral cavity of mammals and belonging to the genera Alysiella , Simonsiella and Conchiformibius. Firstly, by...
Leptospira strains were isolated from freshwater sampled at four sites in Algeria and characterized by whole-genome sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The cells were spiral-shaped and motile. Phylogenetic and MALDI-TOF MS analyses showed that the strains can be clearly disting...
Pathogenic Leptospira are the causative agents of leptospirosis, the most widespread zoonotic infectious disease. Leptospirosis is a potentially severe and life-threatening emerging disease with highest burden in sub-tropical areas and impoverished populations. Mechanisms allowing pathogenic Leptospira to survive inside a host and induce acute lept...
Fragment-based lead discovery has emerged over the last decades as one of the most powerful techniques for identifying starting chemical matter to target specific proteins or nucleic acids in vitro. However, the use of such low-molecular-weight fragment molecules in cell-based phenotypic assays has been historically avoided because of concerns that...
Exopolysaccharide (EPS) layers on the bacterial cell surface are key determinants of biofilm establishment and maintenance, leading to the formation of higher‐order 3D structures that confer numerous survival benefits to a cell community. In addition to a specific cell‐associated EPS glycocalyx, we recently revealed that the social δ‐proteobacteriu...
Experimental evolution of persistence during Mycobacterium canettii infections of mice sheds light on the origins of virulence in ancestral Mycobacterium tuberculosis.
Leptospira dzianensis and Leptospira putramalaysiae were recently described as novel species and published almost concurrently with Leptospira yasudae and Leptospira stimsonii . Genome comparisons based on average nucleotide identity of the type strain genomes indicate that L. dzianensis and L. putramalaysiae are conspecific with L. yasudae and L....
Neisseria meningitidis and Neisseria gonorrhoeae, two highly related species that may have emerged from a common commensal ancestor, constitute major human threats. Vaccines are available to prevent N. meningitidis infection, whereas for N. gonorrhoeae, there are only a limited number of antibiotics available. Unfortunately, some strains of these s...
Background
The evolution of bacteria is shaped by different mechanisms such as mutation, gene deletion, duplication, or insertion of foreign DNA among others. These genetic changes can accumulate in the descendants as a result of natural selection. Using phylogeny and genome comparisons, evolutionary paths can be somehow retraced, with recent event...
Global warming has been associated with increased episodes of mass mortality events in invertebrates, most notably in bivalves. Although the spread of pathogens is one of multiple factors that contribute to such mass mortality events, we don't fully understand the pathophysiological consequences of sea warming on invertebrates. In this work, we sho...
In bacteria, DNA methylation can be facilitated by ‘orphan’ DNA methyltransferases lacking cognate restriction endonucleases, but whether and how these enzymes control key cellular processes are poorly understood. The effects of a specific modification, 4-methylcytosine (4mC), are even less clear, as this epigenetic marker is unique to bacteria and...
Pathogenic Leptospira are the causative agents of leptospirosis, the most widespread zoonotic infectious disease. Leptospirosis is a potentially severe and life-threatening emerging disease with highest burden in sub-tropical areas and impoverish populations. Mechanisms allowing pathogenic Leptospira to survive inside a host and induce acute leptos...
Bacterial surface exopolysaccharide (EPS) layers are key determinants of biofilm establishment and maintenance, leading to the formation of higher-order 3D structures conferring numerous survival benefits to a cell community. In addition to a specific EPS glycocalyx, we recently revealed that the social δ-proteobacterium Myxococcus xanthus secretes...
It has been previously shown that RskA, the anti-Sigma factor K of Mycobacterium tuberculosis, inhibits SigK and that mutations in RskA promote high expression of the SigK regulon. The latter observation led us to hypothesize that RskA mutations lead to loss of the anti-Sigma factor function. In this report, we used natural and artificial mutations...
The pretreatment of biomass remains a critical requirement for bio-renewable fuel production from lignocellulose. Although current processes primarily involve chemical and physical approaches, the biological breakdown of lignin using enzymes and microorganisms is quickly becoming an interesting eco-friendly alternative to classical processes. As a...
The pretreatment of biomass is a critical requirement of bio-renewable fuel production from lignocellulose. Although current processes primarily involve chemical and physical approaches, the biological breakdown of lignin using enzymes and microorganisms is quickly becoming an interesting eco-friendly alternative to classical processes. As a result...
Serine protease autotransporters of Enterobacteriaceae (SPATEs) are secreted proteins that contribute to virulence and function as proteases, toxins, adhesins, and/or immunomodulators. An extra-intestinal pathogenic E. coli (ExPEC) O1:K1 strain, QT598, isolated from a turkey, was shown to contain vat, tsh, and three uncharacterized SPATE-encoding g...
The causative agents of leptospirosis are responsible for an emerging zoonotic disease worldwide. One of the major routes of transmission for leptospirosis is the natural environment contaminated with the urine of a wide range of reservoir animals. Soils and surface waters also host a high diversity of non-pathogenic Leptospira and species for whic...
Although OMVs secreted by Gram-negative bacteria fulfill multiple functions, the molecular mechanism of OMV biogenesis remains ill defined. Our group has previously shown that PmrC (also known as EptA) and CptA maintain OM integrity and provide resistance to iron toxicity and antibiotics in the murine pathogen Citrobacter rodentium . In several ent...
Mycobacteria are well known for their taxonomic diversity, their impact on global health, and for their atypical cell wall and envelope. In addition to a cytoplasmic membrane and a peptidoglycan layer, the cell envelope of members of the order Corynebacteriales, which include Mycobacterium tuberculosis, also have an arabinogalactan layer connecting...
Leptospira is a phylogenetically unique group of bacteria, and includes the causative agents of leptospirosis, the most globally prevalent zoonosis. Bacteriophages in Leptospira are largely unexplored. To date, a genomic sequence is available for only one temperate leptophage called LE1. Here, we sequenced and analysed the first genomes of the lyti...
Metal acquisition is crucial for all cells and for the virulence of many bacterial pathogens. In particular, nickel is a virulence determinant for the human gastric pathogen Helicobacter pylori as it is the cofactor of two enzymes essential for in vivo colonization, urease and a [NiFe] hydrogenase. To import nickel despite its scarcity in the human...
Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM). We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and F...
Formaldehyde is the simplest of all aldehydes and is highly cytotoxic. Its use and associated dangers from environmental exposure have been well documented. Detoxification systems for formaldehyde are found throughout the biological world and they are especially important in methylotrophic bacteria, which generate this compound as part of their met...
Bacterial cells are encompassed by a macromolecular network of peptidoglycan, the major component of bacterial cell walls that provides the cell wall strength and determines bacterial morphology. Eukaryotic organisms sense the presence of bacteria by detecting peptidoglycan fragments shed by the bacterium or released through hydrolytic attack by ho...
Respiratory infectious diseases are the third cause of worldwide death. The nasopharynx is the portal of entry and the ecological niche of many microorganisms, of which some are pathogenic to humans, such as Neisseria meningitidis and Moraxella catarrhalis. These microbes possess several surface structures that interact with the actors of the innat...
By phylogenetic analysis, M. kansasii is closely related to M. tuberculosis. Yet, while both organisms cause pulmonary disease, M. tuberculosis is a global health menace, whereas M. kansasii is an opportunistic pathogen. To illuminate the differences between these organisms, we have sequenced the genome of M. kansasii ATCC 12478 and its plasmid (pM...
By phylogenetic analysis, M. kansasii is closely related to M. tuberculosis. Yet, while both organisms cause pulmonary disease, M. tuberculosis is a global health menace, whereas M. kansasii is an opportunistic pathogen. To illuminate the differences between these organisms, we have sequenced the genome of M. kansasii ATCC 12478 and its plasmid (pM...
Leptospira (L.) interrogans are bacteria responsible for a worldwide reemerging zoonosis. Some animals asymptomatically carry L. interrogans in their kidneys and excrete bacteria in their urine, which contaminates the environment. Humans are infected through skin contact with leptospires and develop mild to severe leptospirosis. Previous attempts t...
Peptidoglycan O-acetylesterase (Ape1), which is required for host survival in Neisseria sp., belongs to the diverse SGNH hydrolase superfamily, which includes important viral and bacterial virulence factors. Here, multi-domain crystal structures of Ape1 with an SGNH catalytic domain and a newly identified putative peptidoglycan-detection module are...
Transition metals such as iron, manganese, and zinc are essential micronutrients for bacteria. However, at high concentration, they can generate non-functional proteins or toxic compounds. Metal metabolism is therefore regulated to prevent shortage or overload, both of which can impair cell survival. In addition, equilibrium among these metals has...
Helicobacter pylori is a human-specific pathogen that exclusively inhabits the human gastric mucosa. However, occasionally, humans transmit H. pylori to susceptible animal hosts bred in colonies. Here, we report the genome sequence of strain X47-2AL, isolated from a domestic
cat and used in anti-H. pylori immunization studies.
The environment is the likely source of many pathogenic mycobacterial species but detection of mycobacteria by bacteriological tools is generally difficult and time-consuming. Consequently, several molecular targets based on the sequences of housekeeping genes, non-functional RNA and structural ribosomal RNAs have been proposed for the detection an...
Mycobacteria produce an unusual, glycolylated form of muramyl dipeptide (MDP) that is more potent and efficacious at inducing
NOD2-mediated host responses. We tested the importance of this modified form of MDP in Mycobacterium tuberculosis by disrupting the gene, namH, responsible for this modification. In vitro, the namH mutant did not produce N-g...
Meningococcal disease occurs as sporadic cases in developed countries, with the occasional emergence of new clones of Neisseria meningitidis. Here, we report the genome sequence of N. meningitidis strain LNP27256, an isolate of sequence type 11 linked to a recent outbreak among men who have sex with men in Europe.
Meningococcal gyrA gene sequence data, MICs, and mouse infection were used to define the ciprofloxacin breakpoint for Neisseria meningitidis. Residue T91 or D95 of GyrA was altered in all meningococcal isolates with MICs of ≥0.064 μg/ml but not among isolates with
MICs of ≤0.032 μg/ml. Experimental infection of ciprofloxacin-treated mice showed slo...
Peptidoglycan O-acetylation is a modification found in many bacteria. In Gram-positive pathogens, it contributes to virulence by conferring resistance to host lysozyme. However, in Gram-negative pathogens, its contribution to physiology and virulence is unknown. We examined the contribution of patA, patB and ape1 to peptidoglycan O-acetylation in t...
Meningococcal disease occurs as sporadic cases in developed countries, with the occasional emergence of new clones of Neisseria meningitidis. Here, we report the genome sequence of N. meningitidis strain LNP27256, an isolate of sequence type 11 linked to a recent outbreak among men who have sex with men in Europe.
Disk assay of bacterial sensitivity to tBOOH (organic peroxyde) for: A) E. coli EMG2 harboring the empty plasmid, pBAD encoding MntXXc or pBAD encoding MntXNm. In this case, this assay as been done in presence of L-arabinose (0.2%). B) X. campestris wild type and mutant lacking mntX. C) N. meningitidis wild type, mutant lacking mntX and complemente...
Missregulation of Fur-regulated genes in low Fe/high Mn conditions for N. meningitidis lacking MntX. Expression quantified by qRT-PCR, of selected genes for N. meningitidis wild type (black) or ΔmntX (white) growth during 6h in GCB with 12.5 µM Desferal and with 25 µM MnCl2. gyrA was used as the endogenous house keeping gene whereas the reference i...
Clinical isolates description.
(XLS)
Analyses of PmntH-luc activity in the presence of increasing amount of Mn A) or Fe B) indicated no impact of N. meningitidis MntX on the regulation mediated by Fe. Results are expressed in % of the maximal induction observed with DP alone.
(EPS)
Disk assay of bacterial sensitivity to 1M MnCl2 for X. campestris wild type and mutants lacking all combination of mntH, mntR or mntX.
(EPS)
Phylogenetic patterns of MntX sequence conservation. A) MntX family tree topology established by the Neighbor-Joining method using unequal rate of evolution across sites and tested with 3000 bootstrap resampling. Tree branch colors reflect the taxonomic distribution of the sequences sampled: proteobacteria from α-, β-, γ-, δ- and ε-divisions; Gram...
Neisseria meningitidis (Nm) and N. gonorrhoeae (Ng) are adapted to different environments within their human host. If the basis of this difference has not yet been fully understood, previous studies (including our own data) have reported that, unlike Ng, Nm tolerates high manganese concentrations. As transition metals are essential regulators of ce...
When studied from the perspective of non-tuberculous mycobacteria (NTM) it is apparent that Mycobacterium tuberculosis has undergone a biphasic evolutionary process involving genome expansion (gene acquisition and duplication) and reductive evolution (deletions). This scheme can instruct descriptive and experimental studies that determine the impor...
In the past decade, the availability of complete genome sequence data has greatly facilitated comparative genomic research aimed at addressing genetic variability within species. More recently, analysis across species has become feasible, especially in genera where genome sequencing projects of multiple species have been initiated. To understand th...
Additional Figures S1 to S5. The file provided different supplementary Figures: S1: Frequency histogram of the distribution of blast scores; S2: Screenshot of mycoHIT; S3: Table representing the number of amino acid differences among the 20 housekeeping genes; S4: Graphic representation of HGT clusters; S5: Number and proportion of genes from Lists...
Potential M. tuberculosis genes deletion. The file provided the protocol and the results to detect genes potentially deleted from the M. tuberculosis ancestor at each strata of its evolution (Lists Bd, Cd, Dd).
Peptidoglycan-derived muramyl dipeptide (MDP) activates innate immunity via the host sensor NOD2. Although MDP is N-acetylated in most bacteria, mycobacteria and related Actinomycetes convert their MDP to an N-glycolylated form through the action of N-acetyl muramic acid hydroxylase (NamH). We used a combination of bacterial genetics and synthetic...
The mycobacteria genus comprises bacteria pathogenic for humans and animals, including M. tuberculosis complex (MTC). In the past decade, considerable research has focused on genomic studies differences between MTC strains and sub-species. These data largely address the devolution of MTC organisms, through a process of reductive genomics and single...
NOD2/CARD15 mediates innate immune responses to mycobacterial infection. However, its role in the regulation of adaptive immunity has remained unknown. In this study, we examined host defense, T cell responses, and tissue pathology in two models of pulmonary mycobacterial infection, using wild-type and Nod2-deficient mice. During the early phase of...
Previous studies have established that members of the Mycobacterium tuberculosis complex exhibit variable production of the antigenic proteins MPT70 and MPT83 due to mutations in their positive regulator,
SigK (sigma factor K), and their negative regulator, RskA (regulator of sigma K). To further understand this highly specific
SigK-controlled regu...
The natural resistance-associated macrophage protein (Nramp) family is functionally conserved in bacteria and eukarya; Nramp homologues function as proton-dependent membrane transporters of divalent metals. Sequence analyses indicate that five phylogenetic groups comprise the Nramp family, three bacterial and two eukaryotic, which are distinct from...
The natural resistance-associated macrophage protein (Nramp) defines a conserved family of secondary metal transporters. Molecular evolutionary analysis of the Nramp family revealed the early duplication of an ancestral eukaryotic Nramp gene, which was likely derived from a bacterial ortholog and characterized as a proton-dependent manganese transp...
