Global population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei.

Shigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring the spread of resistant clones, including those that have recently emerged, at local and global scales

Eukaryotic DNA Polymerases: Proposal for a Revised Nomenclature

Pol polymeraseIn 1975, a Greek letter nomenclature system was introduced to designate DNA polymerases from mammalian cells (1). Ten years ago, progress in the biochemical analysis of eukaryotic DNA polymerases and in the isolation of their genes, particularly in the yeast Saccharomyces cerevisiae, necessitated a revision of the Greek letter nomenclature system and an expansion to include all eukaryotic organisms (2). Until a few years ago, this system sufficed to designate the six known DNA polymerases α, β, γ, δ, ε, and ζ

A role for gut-associated lymphoid tissue in shaping the human B cell repertoire

PMCID: PMC3754866Rockefeller University Press grants the public the non-exclusive right to copy, distribute, or display this Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode

The Genome of Anopheles darlingi, the main neotropical malaria vector

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vectorhuman and vectorparasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles- darlingi. © 2013 The Author(s)

La contamination humaine par Salmonella enterica subsp arizonae a-t-elle un lien avec son émergence dans la filière avicole ?: Salmonella arizonae dans la filière avicole

National audienceSalmonellosis is the second cause of food-borne bacterial illnesses in Europe. Salmonella enterica is a most pathogenic species and can colonize humans, animals, plants and the environment. Subspecies enterica is generally found in farm animals (poultry, pigs, cattle), while the subspecies arizonae is mainly associated with cold-blooded animals. Nevertheless, an increase in human cases of Salmonella enterica subsp. arizonae (serotype: 48:z4,z23:-) has been reported since 2018 with no identified reason. This increase has also been observed in the poultry production, which constitutes a risk for humans. The aim of this project is to use whole genome sequencing (WGS) to determine if there is a phylogenetic link between poultry and human strains. Strains isolated from humans available at the “Institut Pasteur (CNR-ESS)” and strains isolated from the poultry production (NRL Salmonella) were compared using whole genome sequencing data, via a cgMLST analysis carried out by the online database EnteroBase. The results confirmed the emergence of this serotype in poultry production and humans in France and highlighted potential epidemiological links between strains.Les salmonelloses représentent la deuxième cause de maladie bactérienne d’origine alimentaire en Europe. A travers toutes les espèces, Salmonella enterica représente une espèce particulièrement pathogène, elle peut coloniser les humains, les animaux, les plantes et se retrouver dans l’environnement. La sous-espèce enterica est généralement présente chez les mammifères alors que la sous espèce arizonae est principalement associée aux animaux à sang froid. Toutefois, il est notifié depuis 2018 une augmentation des cas humains à Salmonella enterica subsp. arizonae (sérotype : 48:z4,z23:-) sans raison identifiée. Cette augmentation est également observée dans la filière avicole, ce qui constitue un risque pour l’Homme. Ce projet a pour objectif d’analyser le possible lien génomique des souches isolées chez l’Homme et dans la volaille. Dans ce but, des souches issues de cas humains disponibles à l’institut Pasteur (CNR-ESS) et des souches issues de la filière avicole (LNR Salmonella) ont été comparées entre elles à partir des données de séquençage de leur génome, via une analyse cgMLST réalisée par l’intermédiaire de la base de données accessibles en ligne EnteroBase. Les résultats ont permis de confirmer l’émergence de ce sérotype dans la filière avicole et chez l’homme en France et de mettre en évidence de potentiels liens épidémiologiques entre les souches

Global population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei

Shigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring the spread of resistant clones, including those that have recently emerged, at local and global scales

Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting

International audienceMemory B cells (MBCs) can persist for a lifetime, but the mechanisms that allow their long-term survival remain poorly understood. Here, we isolated and analyzed human splenic smallpox/vaccinia protein B5-specific MBCs in individuals who were vaccinated more than 40 years ago. Only a handful of clones persisted over such an extended period, and they displayed limited intra-clonal diversity with signs of extensive affinity-based selection. These long-lived MBCs appeared enriched in a CD21hiCD20hi IgG+ splenic B cell subset displaying a marginal-zone-like NOTCH/MYC-driven signature, but they did not harbor a unique longevity-associated transcriptional or metabolic profile. Finally, the telomeres of B5-specific, long-lived MBCs were longer than those in patient-paired naive B cells in all the samples analyzed. Overall, these results imply that separate mechanisms such as early telomere elongation, affinity selection during the contraction phase, and access to a specific niche contribute to ensuring the functional longevity of MBCs