Polymorphism in the LcrV Antigen Enables Immune Escape From the Protection Conferred by an LcrV-Secreting in a Pseudotuberculosis Mouse Model.

Yersinioses caused by , and are significant concerns in human and veterinary health. The link between virulence and the potent LcrV antigen has prompted the latter's selection as a major component of anti- vaccines. Here, we report that (i) the group of species encompassing and produces at least five different clades of LcrV and (ii) vaccination of mice with an LcrV-secreting only protected against strains producing the same LcrV clade as that of used for vaccination.

Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC.

The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking.

Flagellin-Mediated Protection against Intestinal Yersinia pseudotuberculosis Infection Does Not Require Interleukin-22.

Signaling through Toll-like receptors (TLRs), the main receptors in innate immunity, is essential for the defense of mucosal surfaces. It was previously shown that systemic TLR5 stimulation by bacterial flagellin induces an immediate, transient interleukin-22 (IL-22)-dependent antimicrobial response to bacterial or viral infections of the mucosa. This process was dependent on the activation of type 3 innate lymphoid cells (ILCs).

Characterization of the protective immune response to Yersinia pseudotuberculosis infection in mice vaccinated with an LcrV-secreting strain of Lactococcus lactis.

Background: Pseudotuberculosis is an infection caused by the bacterial enteropathogen Yersinia pseudotuberculosis and is considered to be a significant problem in veterinary medicine. We previously found that intranasal administration of a recombinant Lactococcus lactis strain that secretes the low-calcium response V (LcrV) antigen from Y. pseudotuberculosis (Ll-LcrV) confers protection against a lethal Y.

Evaluation of the Role of the opgGH Operon in Yersinia pseudotuberculosis and Its Deletion during the Emergence of Yersinia pestis.

The opgGH operon encodes glucosyltransferases that synthesize osmoregulated periplasmic glucans (OPGs) from UDP-glucose, using acyl carrier protein (ACP) as a cofactor. OPGs are required for motility, biofilm formation, and virulence in various bacteria. OpgH also sequesters FtsZ in order to regulate cell size according to nutrient availability.

Superantigenic Yersinia pseudotuberculosis induces the expression of granzymes and perforin by CD4+ T cells.

Bacterial superantigens (SAgs) are immunostimulatory toxins that induce acute diseases mainly through the massive release of inflammatory cytokines. Yersinia pseudotuberculosis is the only Gram-negative bacterium known to produce a SAg (Y. pseudotuberculosis-derived mitogen [YPM]).

Proposed reclassification of Pasteurella lymphangitidis Sneath & Stevens 1990 as Yersinia pseudotuberculosis.

The 16S rRNA gene sequences of Pasteurella lymphangitidis, Yersinia pseudotuberculosis and Yersinia pestis were found to be identical and multilocus sequence analysis could not discriminate between the three species. The susceptibility to a Y. pseudotuberculosis phage and the presence of the Y.

Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague.

Potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. We compared the efficacy of a ciprofloxacin (CIN) and gentamicin (GEN) combination therapy with that of each antibiotic administered alone (i) against Yersinia pestis in vitro and (ii) in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h). In vitro, the CIN+GEN combination was synergistic at 0.

In silico comparison of Yersinia pestis and Yersinia pseudotuberculosis transcriptomes reveals a higher expression level of crucial virulence determinants in the plague bacillus.

Although Yersinia pestis and Yersinia pseudotuberculosis are genetically very similar (97% nucleotide sequence identity for most of the chromosomal genes), they exhibit very different patterns of infection. Y. pestis causes plague which is usually fatal in the absence of treatment, whereas Y.

Characterizing consumer health terminology in the breast cancer field.

Despite the large availability of medical information on the Internet, health consumers still encounter problems to find, interpret and understand this information. These problems are mainly due to their lack in medical knowledge and the difference between their language and the language of health professionals. In order to propose information retrieval services more adapted to health consumers language and knowledge, we have developed techniques to collect, identify and analyze the terms and the expressions used by lay persons to talk about breast cancer.

Autophagosomes can support Yersinia pseudotuberculosis replication in macrophages.

Yersinia pseudotuberculosis is able to replicate inside macrophages. However, the intracellular trafficking of the pathogen after its entry into the macrophage remains poorly understood. Using in vitro infected bone marrow-derived macrophages, we show that Y.

Hypoxic single-pass isolated hepatic perfusion of hypotonic Cisplatin: safety study in the pig.

Background: Isolated hepatic perfusion (IHP) of chemotherapy has been proposed to deliver high doses of drug while avoiding systemic toxicity. Hypotonic cisplatin has a high in vitro activity on human colon cancer cells. We studied the safety of a 30-min hypoxic single-pass IHP with hypotonic cisplatin.

An iron-regulated LysR-type element mediates antimicrobial peptide resistance and virulence in Yersinia pseudotuberculosis.

During the course of its infection of the mammalian digestive tract, the entero-invasive, Gram-negative bacterium Yersinia pseudotuberculosis must overcome various hostile living conditions (notably, iron starvation and the presence of antimicrobial compounds produced in situ). We have previously reported that in vitro bacterial growth during iron deprivation raises resistance to the antimicrobial peptide polymyxin B; here, we show that this phenotype is mediated by a chromosomal gene (YPTB0333) encoding a transcriptional regulator from the LysR family. We determined that the product of YPTB0333 is a pleiotropic regulator which controls (in addition to its own expression) genes encoding the Yfe iron-uptake system and polymyxin B resistance.

Protection against Yersinia pseudotuberculosis infection conferred by a Lactococcus lactis mucosal delivery vector secreting LcrV.

Herein, we sought to evaluate the potential of a recombinant Lactococcus lactis strain secreting the Yersinia pseudotuberculosis low-calcium response V (LcrV) antigen for mucosal vaccination against Yersinia infections. We showed that the recombinant strain induced specific systemic and mucosal antibody and cellular immune responses after intranasal immunization and protected mice against both oral and systemic Y. pseudotuberculosis infections.

Growth of Yersinia pseudotuberculosis in human plasma: impacts on virulence and metabolic gene expression.

Background: In man, infection by the Gram-negative enteropathogen Yersinia pseudotuberculosis is usually limited to the terminal ileum. However, in immunocompromised patients, the microorganism may disseminate from the digestive tract and thus cause a systemic infection with septicemia.

Results: To gain insight into the metabolic pathways and virulence factors expressed by the bacterium at the blood stage of pseudotuberculosis, we compared the overall gene transcription patterns (the transcriptome) of bacterial cells cultured in either human plasma or Luria-Bertani medium.

Sudden onset of pseudotuberculosis in humans, France, 2004-05.

Cases of Yersinia pseudotuberculosis infection increased in France during the winter of 2004-05 in the absence of epidemiologic links between patients or strains. This increase represents transient amplification of a pathogen endemic to the area and may be related to increased prevalence of the pathogen in rodent reservoirs.

Therapeutic potential of Yersinia anti-inflammatory components.

Microbial pathogens have developed various stratagems for modulating and/or circumventing the host's innate and adaptive immunity. Hence, certain virulence factors can be viewed as potential therapeutic agents for human immunopathological diseases. This is the case for virulence plasmid-encoded proteins from pathogenic Yersiniae that inhibit the host's inflammatory response by interfering with various cellular signaling pathways.

Two-component system regulon plasticity in bacteria: a concept emerging from phenotypic analysis of Yersinia pseudotuberculosis response regulator mutants.

In bacteria, the most rapid and efficient means of adapting gene transcription to extracellular stresses often involves sophisticated systems referred to as two-component systems (2CSs). Although highly conserved throughout the bacterial world, some of these systems may control distinct cell events and have differing contributions to virulence, depending on the species considered. This chapter summarizes the work performed by our group--from the initial PhoP-PhoQ and PmrA-PmrB studies to the most recent genome-scale preliminary analyses--in an attempt to highlight the contribution of 2CS regulon plasticity to the acquisition of some of Yersinia pseudotuberculosis' specific features.

Transcriptome analysis of Yersinia pestis in human plasma: an approach for discovering bacterial genes involved in septicaemic plague.

Yersinia pestis is the aetiologic agent of plague. Without appropriate treatment, the pathogen rapidly causes septicaemia, the terminal and fatal phase of the disease. In order to identify bacterial genes which are essential during septicaemic plague in humans, we performed a transcriptome analysis on the fully virulent Y.

Phenotypic analysis of Yersinia pseudotuberculosis 32777 response regulator mutants: new insights into two-component system regulon plasticity in bacteria.

Two-component regulatory systems (2CSs) typically comprise a sensor kinase and a response regulator that, in concert, monitor the concentration of particular extracellular factors and mediate the transcription of specific genes accordingly. As such, 2CSs play an important role in the regulation of bacterial pathogenesis. On the basis of genome-wide in silico analysis, the Gram-negative enteropathogenic bacterium Yersinia pseudotuberculosis is thought to encode 24 complete 2CSs.

Prevention and treatment of colitis with Lactococcus lactis secreting the immunomodulatory Yersinia LcrV protein.

Background & Aims: The low calcium response V (LcrV) protein synthesized by gram-negative, pathogenic yersiniae participates in bacterial evasion of the host's innate immune response by stimulating synthesis of the anti-inflammatory interleukin (IL)-10 and preventing the activation of proinflammatory cytokines.

Methods: We genetically engineered the food-grade bacterium Lactococcus lactis to secrete the LcrV protein from the enteropathogenic species Yersinia pseudotuberculosis. The protective and therapeutic potential of orally administered LcrV-secreting L lactis was evaluated in 2 models of acute experimental colitis (induced by trinitrobenzene sulfonic acid [TNBS] and dextran sodium sulfate [DSS], respectively) in wild-type and knockout mice.

Similarities of Kawasaki disease and Yersinia pseudotuberculosis infection epidemiology.

Although an infectious etiology is strongly suspected in Kawasaki disease (KD), an etiologic agent has not yet been identified. By reviewing epidemiologic data published in past decades, this work highlights a higher incidence of KD when populations were exposed to the risk of Yersinia pseudotuberculosis infection. This hitherto unnoticed element reinforces the hypothesis whereby this bacterium might contribute to the development of KD in some cases.

NODs in defence: from vulnerable antimicrobial peptides to chronic inflammation.

Defensins and cathelicidins are prevalent and essential gastrointestinal cationic antimicrobial peptides (CAPs). However, these defensive peptides are not infallible because certain enteropathogens can overcome their protective function. Furthermore, impaired defensin synthesis has been linked to the occurrence of Crohn's disease (CD), a chronic inflammatory bowel disease.

High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis.

Objective: To investigate the role of increased intra-abdominal pressure (IAP) on the intratumoral accumulation and the antitumor effect of intraperitoneal cisplatin in rats with advanced peritoneal carcinomatosis. To evaluate the tolerance of IAP in pigs, as it is a large animal with a body size equivalent to humans.

Summary Background Data: To investigate if an active convection, driven by a positive IAP, increases cisplatin penetration and antitumor effectiveness in a model of advanced peritoneal carcinomatosis in rats.