Project description:Design: double blind controlled randomized trial with a parallel design and 3 treatment groups Description of subjects: Patients admitted in study centers for colorectal surgery under laporoscopy and/or laparotomy.
Product:
Product 1: BB536 and LA1 (10E9) Product 2: BB536 and LA1 (10E7) Placebo: Maltodextrin Number of patients: enrolled subjects: n=33, ITT data set: n=31, PP data set: n=30
Primary objective:
Colonization (biopsy+stools) of each bacteria for one of the dose at D0 (surgical procedure)
Secondary objectives:
* Influence of the probiotic bacteria on the gut microflora
* Modulation of the immune and inflammatory response
Additional objectives:
* Investigate dose effect on La1 colonization
* Investigate the effect of La1 colonization, treatment without La1 colonization, and absence of treatment and La1 colonization on other bacteria and on immunological parameters
Project description:Chronic infection of the human stomach with Helicobacter pylori leads to a variety of pathologic sequelae including peptic ulcer and gastric cancer, resulting in significant human morbidity and mortality. Several genes have been implicated in disease related to H. pylori infection including the vacuolating cytotoxin and the cag pathogenicity island. Other factors important for establishment and maintenance of infection include urease enzyme production, motility, iron uptake and stress response. We utilized a C57BL/6 mouse infection model to query a collection of 2400 transposon mutants in two different bacterial strain backgrounds for H. pylori genetic loci contributing to colonization of the stomach. Microarray based tracking of transposon mutants allowed us to monitor the behavior of transposon insertions in 758 different gene loci. Of the loci measured 223 (29%) had a predicted colonization defect. These include previously described H. pylori virulence genes, genes implicated in virulence in other pathogenic bacteria and 81 hypothetical proteins. We have retested 10 previously uncharacterized candidate colonization gene loci by making independent null alleles and confirmed their colonization phenotype using competition experiments and determination of the dose required for 50% infection. Of the genetic loci retested, 60% have strain specific colonization defects while 40% had phenotypes in both strain backgrounds for infection, highlighting the profound effect of H. pylori strain variation on the pathogenic potential of this organism. This SuperSeries is composed of the SubSeries listed below.
Project description:Transcriptional profiling of the zebrafish embryonic host response to infection by injection of 200 CFUs of Edwardsiella tarda (strain FL6-60) All infection experiments were performed using mixed egg clutches of Albino strain zebrafish. Embryos were staged at 28 hours post fertilization (hpf) by morphological criteria and approximately 200 cfu of mCherry expressing E. tarda bacteria were injected into the caudal vein close to the urogenital opening. As a control an equal volume of PBS was likewise injected. Single embryos of the infected and control group were collected 8 hours post infection (hpi).
Project description:The infection with the intracellular pathogen Listerial monocytogenes in mice is well characterized resulting in bacterial colonization of various organs, mediated cellular response, and its role in the subsequent clearace of the bacteria, have been well described. In order to comprehensively describe the course of infection and identify molecular events leading to control of infection, we have undertaken whole organ profiling of the mouse spleen after infection. Keywords: L. monocytogenes infection, spleen, microarray
Project description:Intracellular pathogens such as Listeria monocytogenes subvert cellular functions through the interaction of bacterial effectors with host components. Here we found that a secreted listerial virulence factor, LntA, could target the chromatin repressor BAHD1 in the host cell nucleus to activate IFN-stimulated genes (ISGs). IFN-λ expression was induced in response to infection of epithelial cells with bacteria lacking LntA; however, the BAHD1-chromatin associated complex repressed downstream ISGs. In contrast, in cells infected with lntA-expressing bacteria, LntA prevented BAHD1 recruitment to ISGs and stimulated their expression. Murine listeriosis decreased in BAHD1+/- mice or when lntA was constitutively expressed. Thus the LntA-BAHD1 interplay may modulate IFN-λ−mediated immune response to control bacterial colonization of the host. In this dataset, we include the expression data obtained following infection of human Lovo cells infected with Listeria bacteria expressing (LntA-V5+) or not (DlntA) the virulence facteur LntA
Project description:Diarrhea remains a major cause of death in children. Current diagnostic methods largely rely on stool culture and suffer from low sensitivity and inadequate specificity, often leading to inappropriate treatment. The objective of the present study was to use RNA sequencing (RNAseq) analysis to determine blood transcriptional profiles specific for several common pathogenic bacteria and viruses that cause diarrhea in children. We collected whole blood samples from children in Mexico having diarrhea associated with a single pathogen and without systemic complications. Our RNAseq data suggested that the blood signatures can differentiate children with diarrhea from healthy children either with or without bacterial colonization. Moreover, we detected different expression profiles from bacterial and viral infection, demonstrating for the first time the use of RNAseq to identify the etiology of infectious diarrhea. Whole blood from 207 children including children with diarrhea caused by rotavirus (n=55), E.coli (n=55), Salmonella (n=36), Shigella (n=37) and control children (n=24).
Project description:Intracellular pathogens such as Listeria monocytogenes subvert cellular functions through the interaction of bacterial effectors with host components. Here we found that a secreted listerial virulence factor, LntA, could target the chromatin repressor BAHD1 in the host cell nucleus to activate IFN-stimulated genes (ISGs). IFN-M-NM-; expression was induced in response to infection of epithelial cells with bacteria lacking LntA; however, the BAHD1-chromatin associated complex repressed downstream ISGs. In contrast, in cells infected with lntA-expressing bacteria, LntA prevented BAHD1 recruitment to ISGs and stimulated their expression. Murine listeriosis decreased in BAHD1+/- mice or when lntA was constitutively expressed. Thus the LntA-BAHD1 interplay may modulate IFN-M-NM-;M-bM-^HM-^Rmediated immune response to control bacterial colonization of the host. In this dataset, we include the expression data obtained following infection of human Lovo cells infected with Listeria bacteria expressing (LntA-V5+) or not (DlntA) the virulence facteur LntA RNA from LoVo cells grown in 6-well plates and infected with either lntAV5+ or lntAM-bM-^@M-^S strains was extracted. Three biological replicates were analyzed for each experimental condition.
Project description:We profiled the expression of circulating microRNAs (miRNAs) in mice exposed to gram-positive and gram-negative bacteria using Illumina small RNA deep sequencing. Recombinant-specific gram-negative pathogen Escherichia coli (Xen14) and gram-positive pathogen Staphylococcus aureus (Xen29) were used to induce bacterial infection in mice at a concentration of 1 × 108 bacteria/100 μL of phosphate buffered saline (PBS). Small RNA libraries generated from the serum of mice after exposure to PBS, Xen14, Xen29, and Xen14+Xen29 via the routes of subcutaneous injection (I), cut wound (C), or under grafted skin (S) were analyzed using an Illumina HiSeq2000 Sequencer. Following exposure to gram-negative bacteria alone, no differentially expressed miRNA was found in the injection, cut, or skin graft models. Exposure to mixed bacteria induced a similar expression pattern of the circulating miRNAs to that induced by gram-positive bacterial infection. Upon gram-positive bacterial infection, 9 miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p, mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p, mir-215-5p) showed upregulation greater than 4-fold with a p-value < 0.01. Among them, mir-193b-3p, mir-133a-1-3p, and mir-133a-2-3p presented the most common miRNA targets expressed in the mice exposed to gram-positive bacterial infection.
Project description:Better understanding of S. aureus throat colonization in the presence of other competing/coexisting microbes may provide insight into S. aureus adaptation to the human throat and recurrence of infection. In this work, we explore the responses triggered by the encounter between two common throat bacteria, S. aureus and S. anginosus, in the presence of human tonsillar epithelial cells. We performed an in vitro coculture experiment followed by RNA sequencing. A total of 332 and 279 significant DEGs with p-value < 0.05 and Log2 fold change > |2| were identified after 1 h and 3 h of post-infection, respectively. Our study identified several transcripts in S. aureus that might be important when facing a potential competitor during throat colonization. These transcripts may be useful in the development of treatments against S. aureus throat colonization and could be further investigated to better understand their roles in the immune response.
Project description:We present a detailed single cell time course of the macrophage response to Salmonella infection. By combining phenotypic fluorescent labels with single cell expression analysis we are able to identify gene modules associated with bacterial exposure and bacterial infection. We also identify other genetic clusters that are expressed heterogenously, ananlyzing both their regulation and their impact on infection Analysis of 192 single cells across 4 time points after Salmonella exposure (MOI 1:1) with one of three different fluorescent labels indicating whether a given cell contained no intracellular bacteria (non-fluorescent), contained dead intracellular bacteria (only pHrodo positive), or contained live intracellular bacteria (pHrodo and GFP positive)