A chromosomally integrated bacteriophage in invasive meningococci

Cerebrospinal meningitis is a feared disease that can cause the death of a previously healthy individual within hours. Paradoxically, the causative agent, Neisseria meningitidis, is a common inhabitant of the human nasopharynx, and as such, may be considered a normal, commensal organism. Only in a small proportion of colonized people do the bacteria invade the bloodstream, from where they can cross the blood–brain barrier to cause meningitis. Furthermore, most meningococcal disease is caused by bacteria belonging to only a few of the phylogenetic groups among the large number that constitute the population structure of this genetically variable organism. However, the genetic basis for the differences in pathogenic potential remains elusive. By performing whole genome comparisons of a large collection of meningococcal isolates of defined pathogenic potential we brought to light a meningococcal prophage present in disease-causing bacteria. The phage, of the filamentous family, excises from the chromosome and is secreted from the bacteria via the type IV pilin secretin. Therefore, this element, by spreading among the population, may promote the development of new epidemic clones of N. meningitidis that are capable of breaking the normal commensal relationship with humans and causing invasive disease

Association of a Bacteriophage with Meningococcal Disease in Young Adults

Despite being the agent of life-threatening meningitis, Neisseria meningitidis is usually carried asymptomatically in the nasopharynx of humans and only occasionally causes disease. The genetic bases for virulence have not been entirely elucidated and the search for new virulence factors in this species is hampered by the lack of an animal model representative of the human disease. As an alternative strategy we employ a molecular epidemiological approach to establish a statistical association of a candidate virulence gene with disease in the human population. We examine the distribution of a previously-identified genetic element, a temperate bacteriophage, in 1288 meningococci isolated from cases of disease and asymptomatic carriage. The phage was over-represented in disease isolates from young adults indicating that it may contribute to invasive disease in this age group. Further statistical analysis indicated that between 20% and 45% of the pathogenic potential of the five most common disease-causing meningococcal groups was linked to the presence of the phage. In the absence of an animal model of human disease, this molecular epidemiological approach permitted the estimation of the influence of the candidate virulence factor. Such an approach is particularly valuable in the investigation of exclusively human diseases

A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses

This work was supported by the Ligue contre le Cancer (“Equipe labellisée”), the Fondation Princesse Grace de Monaco, and the European Research Council Advanced grants “Memo-B” (to J.-C. Weill) and “B-response” (to C.-A. Reynaud). L.-H. Thai was supported by a Poste d'Accueil INS ERM.To what extent immune responses against the gut flora are compartmentalized within mucosal tissues in homeostatic conditions remains a much-debated issue. We describe here, based on an inducible AID fate-mapping mouse model, that systemic memory B cell subsets, including mainly IgM+ B cells in spleen, together with IgA+ plasma cells in spleen and bone marrow, are generated in mice in the absence of deliberate immunization. While the IgA component appears dependent on the gut flora, IgM memory B cells are still generated in germ-free mice, albeit to a reduced extent. Clonal relationships and renewal kinetics after anti-CD20 treatment reveal that this long-lasting splenic population is mainly sustained by output of B cell clones persisting in mucosal germinal centers. IgM-secreting hybridomas established from splenic IgM memory B cells showed reactivity against various bacterial isolates and endogenous retroviruses. Ongoing activation of B cells in gut-associated lymphoid tissues thus generates a diversified systemic compartment showing long-lasting clonal persistence and protective capacity against systemic bacterial infections.Publisher PDFPeer reviewe

Implication d'un bactériophage filamenteux dans la virulence de Neisseria meningitidis

Neisseria meningitidis est responsable de méningites et de septicémies mais également une bactérie commensale du rhinopharynx de l'Homme. Des études par MLST montrent que seuls certains complexes clonaux dits hyperinvasifs sont responsables d'infections invasives. La comparaison du génome des souches de CC hyperinvasifs et de souches non hyperinvasifs a permis de mettre en évidence un îlot de 10 gènes qui était significativement associé aux souches hyperinvasives. Une étude sur plus de 1200 souches provenant de malades et de porteurs sains a montré que cet îlot était associé à la maladie au moment de l'adolescence. Cet îlot MDA (Meningococcal Disease Associated) est un bactériophage filamenteux ayant une organisation et un cycle biologique proches de ceux des bactériophages Ff d'Escherichia coli et CTX de Vibrio cholerae. Il en diffère par l'utilisation de la sécrétine PilQ pour sortir ou la présence dans son génome d'une transposase de la famille IS710. La découverte de ce bactériophage filamenteux ouvre des perspectives pour la compréhension de la survenue de maladies invasives au moment de l'adolescence.Despite being the agent of life-threatening meningitis, Neisseria meningitidis is usually carried asymptomatically in the nasopharynx of humans and only occasionally causes disease. The genetic bases for virulence have not been entirely elucidated. As an alternative strategy we employ a molecular epidemiological approach to establish a statistical association of a candidate virulence gene with disease in the human population. We examine the distribution of an island in 1288 meningococci isolated from cases of disease and asymptomatic carriage. This island was over-represented in disease isolates from young adults indicating that it may contribute to invasive disease in this age group. This island, named MDA (" Meningococcal Disease Associated"), corresponds to a filamentous bacteriophage. It has a biological organization and a cycle close to those of the filamentous bacteriophages Ff of Escherichia coli and CTX of Vibrio cholerae. They still differ by the use of the PilQ secretin to go out or presence in its genome of a gene encoding for a transposase. of the IS110 family. The discovery of this filamentous bacteriophage by inverse epidemiology opens new perspectives for the understanding of invasive disease at the time of adolescence.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Caractérisation et étude d'un bactériophage associé à la virulence de Neisseria meningitidis

PARIS-BIUP (751062107) / SudocSudocFranceF

Bacteriophages and pathogenicity: more than just providing a toxin?

International audienceAn increasing number of pathogenicity factors are discovered to be carried by bacteriophages. This review considers the bacteriophage-bacterium interaction and its relation to disease processes. We discuss the search for new bacteriophage-associated pathogenicity factors with emphasis on recent advances brought by the use of genomic sequence data and the techniques of genomic epidemiology

Molecular interactions between Neisseria meningitidis and its human host

International audienc

Bacillus cereus Induces Severe Infections in Preterm Neonates: Implication at the Hospital and Human Milk Bank Level

International audienceHuman breast milk (HBM) is a source of essential nutrients for infants and is particularly recommended for preterm neonates when their own mother's milk is not available. It provides protection against infections and decreases necrotizing enterocolitis and cardiovascular diseases. Nevertheless, HBM spoilage can occur due to contamination by pathogens, and the risk of a shortage of HBM is very often present. B. cereus is the most frequent ubiquitous bacteria responsible for HBM being discarded. It can contaminate HBM at all stages, from its collect point to the storage and delivery. B. cereus can induce severe infection in newborns with very low birth weight, with sometimes fatal outcomes. Although the source of contamination is rarely identified, in some cases, HBM was suspected as a potential source. Even if the risk is low, as infection due to B. cereus in preterm infants should not be overlooked, human milk banks follow strict procedures to avoid contamination, to accurately identify remaining bacteria following pasteurization and to discard non-compliant milk samples. In this review, we present a literature overview of B. cereus infections reported in neonates and the suspected sources of contamination. We highlight the procedures followed by the human milk banks from the collection of the milk to its microbiological characterization in Europe. We also present improved detection and decontamination methods that might help to decrease the risk and to preserve the public's confidence in this vital biological product for infants whose mothers cannot breastfeed

Diffusion communautaire des entérobactéries sécrétrices de β-lactamase à spectre élargi (EBLSE)

Longtemps limitée au milieu hospitalier, l’épidémiologie des entérobactéries sécrétrices de β-lactamase à spectre élargi (EBLSE) s’est considérablement modifiée depuis les années 2000. On assiste depuis à une diffusion des EBLSE en milieu communautaire. Escherichia coli qui sécrète une CTX-M est l’espèce la plus fréquemment isolée. Ce phénomène épidémique est particulièrement inquiétant par la rapidité de sa diffusion et son étendue géographique. La maîtrise du risque passe par la mise en place et le respect des mesures d’hygiène, le dépistage systématique à l’admission dans les unités à haut risque et la maîtrise de la prescription antibiotique. Parmi les β-lactamines, seules les carbapénèmes gardent une efficacité, et doivent donc être réservées aux infections sévères. Du fait de la fréquence des corésistances, peu de molécules restent utilisables pour une attitude d’antibiothérapie probabiliste