We are examining differences within the genomes of E. coli strains.

To perform assignment of 16S sequences to bacterial genera and statistical analysis of variations of bacterial populations collected from mice feces

Assemblage de novo d'une souche bactérienne afin de pourvoir la soumettre dans une plateforme d'annotation.

Context. Bacteria of the genus Shigella and strains of entero-invasive Escherichia coli (EIEC) are responsible of bacillary dysentery (shigellosis) in humans. Although (very) closely related to E. coli, the genus Shigella is divided in four "species": S. boydii, S. dysenteriae, S. flexneri and S. sonnei. Most virulence determinants enabling these bacteria to enter into and disseminate within epithelial cells are encoded by a 200-kb virulence plasmid (VP). The first complete sequence of a VP (pWR100 from a S. flexneri strain of serotype 5a) was determined by our laboratory in 2000. The VP contains genes of different origins, as attested by their G+C content ranging from 30 to 60%, traces of four plasmids and a large numbers of various insertions sequences (IS) representing 30-40% of the total sequence (Buchrieser et al., 2000). In addition to IS sequences, the VP carries members of several multigene families (exhibiting over 90% identity). Such repeated sequences are potentially prone to recombination (allelic exchange, gene conversion) and deletion. Based on the analysis of three genes carried by the VP, it has been proposed that, depending of the species / phylogenetic group, there are two forms of the VP (pInvA & pInvB) that were acquired independently in different original E. coli strains. General questions. What are the architectures of the VP from different phylogenetic groups and how different are pInvA and pInvB ? Which genes are conserved in all VP and which genes are unique to some VP ? Did recombinations occur and, if so, where and when ? To answer these questions, a comparative analysis of the genetic organization and gene conservation among the VP from different phylogenetic groups of Shigella/EIEC has been undertaken using the available complete (or presented as such) sequences of 15 VP, including three members for each of five phylogenetic groups (S. boydii, S. dysenteriae 1, S. flexneri, S. sonnei and EIEC).

Shigella species and E. coli are very closely related bacteria belonging to the Enterobacteriaceae family. Phenotypically they are very similar and genotypically they could be considered the same species. The differentiation of Shigella species from E. coli is a significant diagnostic challenge for the clinical microbiology laboratories. They increasingly use maldi-tof mass spectrometry-based microbial identification systems but the latter are currently not able to distinguish these species. As the National Reference Center of E. coli and Shigella, we possess an exhaustive and extensive collection of strains (all serotypes and a wide range of phenotypic profils). We want to use our unique strain collection to propose a highly performant approach for differentiating these bacterial species by MALDI-TOF MS. Success of this study would be incredibly valuable for making an immediate impact on the clinical microbiology diagnosis.

Nous avons pu montrer grâce au projet de recherche clinique VOYAG’R (PHRC AOR 11101- IP Pr S. Matheron) que les voyages dans une zone tropicale constituaient un risque d’acquérir une Entérobactérie multi-résistante (EMR). Pendant 15 mois, la présence d’EMR a été recherchée chez 574 sujets avant et après leur voyage en zone tropicale. Les voyageurs porteurs au retour étaient suivis sur une période de 12 mois (1, 2, 3, 6 et 12 mois ou jusqu’à négativation). Au cours de leur séjour, la moitié des voyageurs ont acquis une EMR. Nous avons également observé que trois mois après leur retour, 95% des voyageurs avaient éliminé leur EMR. Cependant 11 sujets ont conservé leur(s) souche(s) d’EMR pendant au moins 6 mois. Ces souches persistantes pourraient avoir des capacités pour perdurer au sein du tube digestif

Escherichia coli is one of the major bacterial pathogens that are responsible for numerous nosocomial infections. While most of the E. coli infections are rather related to colonisation of the urinary tract there are rare, but complex to resolve, cases of E. coli infection of central veinous catheter. To determine whether the E. coli strains that colonize central veinous catheters have specific properties we have started a preliminary project where few E. coli strains responsible for such infections have been collected (4 strains) and a comparative phenotypic analysis has been initiated. To deepen this analysis the genome of these 4 strains has been sequenced and we expected to analyse these genomes to identify potential interesting features that can be link to the clinical context of these strains. Notably, it is expected that these strains of E. coli might carry some specific adhesion factors, virulence genes and potential antibiotic resistance. This project could lead to the identification of some interesting factors that can explain their tropism for central veinous catheters. It is envisionned that this project can be expanded to the analysis of more E. coli strains responsible for central veinous catheter-related infections, and thus could open the way for the development of either biological markers of such infection or fighting strategies against catheter-related infections.

Taking advantage of a murine model of controlled microbiota composed of 12 strains, we evaluated the activity of a cocktail of three virulent bacteriophages to target a murine Escherichia coli strain in the mammalian gut.

Bacteriophages infect bacteria. One bacteriophage can infect several strains. Around the world, many labs have performed spot tests to determine the host range of bacteriophages but this information is not accessible because there is no tool to process and store it. Developing such a tool will be useful for the phage community but also for the entire community of virologists.

crispr.pasteur.fr is a website providing resources to visualize CRISPR screen data and design CRISPR experiments in bacteria

We wish to study the genome-wide integration preferences of integron cassettes in the MG1655 Escherichia coli genome.

Ndd expression in E.coli induces nuclear disruption where the nucleoid is swiftly relocated from a central position in the cell to a submembrane location. RNAseq analysis showed Ndd expression induces the differential expression of hundreds of E.coli genes. We would like to see if some of those genes are related to regulation networks of several nucleoid associated proteins.

Severe bacterial infections are a leading cause of neonatal deaths, with low income countries (LICs) bearing the highest burden. In LICs, neonatal bacterial infections are mainly caused by Enterobacteriaceae. One important driver of unfavorable outcome in infections caused by these bacteria is multidrug resistance. Of particular concern, extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) are resistant to most penicillins and especially cephalosporins (3rd-4th generation). Enterobacteriaceae are known to colonize the digestive tract, which represents the first step for potential neonatal infections. The newborn is exposed at birth and during the first weeks of life to several possible sources of ESBL-PE acquisition, e.g. maternal, health-care facilities, and outside hospitals: parents, others relatives, food and environment. However, the routes of ESBL-PE acquisition in neonates are not well defined. Also, local environments and practices influence strongly the interactions of the infant with its environment. However, practices contributing to the transmission of ESBL-PE to neonates are not well characterized in LICs. The objectives of the project are: a better knowledge of the role of different routes of ESBL-PE transmissions to newborns in the community, and more specifically within a household, to understand local environments and practices that facilitate ESBL-PE transmission in Madagascar In Madagascar, 60 newborns and members of their households will be follow-up for one month. ESBL-PE will be characterized with last generation DNA sequencing methods. To integrate all these data globally, we will develop novel sophisticated analytical approaches combining mathematical modeling and statistics. Also, in-depth interviews will be conducted and mother-newborn pairs will be followed with a participants-observations methodology. Our study aims at identifying and quantifying the role of the different routes of transmission for newborns in the community. With a multidisciplinary approach, it should allow identifying the most acceptable interventions for local population to prevent ESBL-PE acquisition in newborns in Madagascar, where the burden of neonatal infection is huge. Partner : Institut Pasteur in Madagascar

Gastrointestinal (GI) cancers are due to over time accumulation of genetic and epigenetic alterations resulting from complex interplay between host, bacterial and environmental factors. Several bacteria have been associated with GI cancers development. Our hypothesis is that GI tumorigenesis likely involves synergistic or sequential impacts of several pathobionts. Based on molecular tracks establishing links between bacteria and host pathways, we aim to understand how several pathobionts co-inhabitation in the same host can modulate their respective pro-tumoral potency. To investigate this, we developed in vivo and in vitro co-infection models to study underlying mechanisms that could promote tumorigenesis.

We want to add/create a similar website to CIRPSR.pasteur.fr to use CRISPR-Cas9 as an antimicrobial.