Toxin release mediated by the novel autolysin Cwp19 in Clostridium difficile

Clostridium difficile, also known as Clostriodioides difficile, is a Gram positive, spore-forming bacterium and a leading cause of antibiotic-associated diarrhea in nosocomial environments. The key virulence factors of this pathogen are two toxins, toxin A and toxin B, released from the cells to the gut and causing colonic injury and inflammation. Although their mechanism of action is well known, the toxins A and B have no peptide signals and their secretion mechanisms involving the holin-like protein TcdE and autolysis are still under active investigation. Autolysis is primarily mediated by peptidoglycan hydrolases, an important group of enzymes that cleave covalent bonds in the cell wall peptidoglycan. Peptidoglycan hydrolases are essential for peptidoglycan remodeling but most of them also have the potential to lyse the cells under various conditions. In a recent report by Wydau-Dematteis et al. (MBio 9(3): e00648-18), we characterized a novel peptidoglycan hydrolase Cwp19 in C. difficile. Importantly, Cwp19 mediates toxins secretion in a glucose-dependent fashion suggesting a potential role in C. difficile pathogenesis. Peptidoglycan hydrolases are not very well characterized in C. difficile despite the important role of these enzymes in cell division and sporulation as shown in model organisms like Bacillus subtilis. In addition, these enzymes can be implicated in pathogenicity as exemplified by the release of pneumococcal virulence factors

Increased sporulation underpins adaptation of Clostridium difficile strain 630 to a biologically–relevant faecal environment, with implications for pathogenicity

Abstract Clostridium difficile virulence is driven primarily by the processes of toxinogenesis and sporulation, however many in vitro experimental systems for studying C. difficile physiology have arguably limited relevance to the human colonic environment. We therefore created a more physiologically–relevant model of the colonic milieu to study gut pathogen biology, incorporating human faecal water (FW) into growth media and assessing the physiological effects of this on C. difficile strain 630. We identified a novel set of C. difficile–derived metabolites in culture supernatants, including hexanoyl– and pentanoyl–amino acid derivatives by LC-MSn. Growth of C. difficile strain 630 in FW media resulted in increased cell length without altering growth rate and RNA sequencing identified 889 transcripts as differentially expressed (p < 0.001). Significantly, up to 300–fold increases in the expression of sporulation–associated genes were observed in FW media–grown cells, along with reductions in motility and toxin genes’ expression. Moreover, the expression of classical stress–response genes did not change, showing that C. difficile is well–adapted to this faecal milieu. Using our novel approach we have shown that interaction with FW causes fundamental changes in C. difficile biology that will lead to increased disease transmissibility

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota

Probabilistic Fire Risk Framework for Optimizing Construction Site Layout

Purpose: This paper aims to develop an efficient model able to reduce catastrophic consequences and the significant number of victims resulting from fires at construction sites. The paper proposes probabilistic modeling aimed to minimize the probability of failure of a construction site. Methodology: The developed model in this paper consists of modeling fire hazards, the vulnerability of the potential targets, and the risk within construction sites. The optimization algorithm called &ldquo;differential evolution&rdquo; is used in order to determine the optimal site layout, which is characterized by having the smallest overall probability of failure. A numerical simulation is performed to delineate an appropriate probability density function of the failure of the site. In addition, a geographic information system (GIS) is used to display the spatial variability of fire risk on a construction site. Findings: The paper provides an efficient model to enhance site layout planning and assign locations for supporting temporary facilities at appropriate positions within a construction site. The model is examined through applying it on a simple case study containing numerous facilities. All these facilities are considered vulnerable targets and some of them are potential fire hazards, with different intensity values. Value: Most of the previous research focuses on travel cost distance in developing site layout planning models. This paper fulfills the development of a valuable model able to generate an optimized construction site layout by minimizing the probability of failure of the whole site. It will assist the decision makers and the risk managers in identifying the riskiest zones on a construction site

Data from: Heterogeneity in efflux pump expression predisposes antibiotic-resistant cells to mutation

Antibiotic resistance is often the result of mutations that block drug activity; however, bacteria also evade antibiotics by transiently expressing genes such as multidrug efflux pumps. A crucial question is whether transient resistance can promote permanent genetic changes. Previous studies have established that antibiotic treatment can select tolerant cells that then mutate to achieve permanent resistance. Whether these mutations result from antibiotic stress or preexist within the population is unclear. To address this question, we focused on the multidrug pump AcrAB-TolC. Using time-lapse microscopy, we found that cells with higher acrAB expression have lower expression of the DNA mismatch repair gene mutS, lower growth rates, and higher mutation frequencies. Thus, transient antibiotic resistance from elevated acrAB expression can promote spontaneous mutations within single cells

Gestion des coordonnées dans les systèmes d'information géographique (développement d'un outil de conversion)

L'identification des systèmes de coordonnées des données SIG et la connaissance des algorithmes de transformation lors du passage d un système vers un autre, disponibles sur les différents logiciels SIG, sont des conditions préalables indispensables à toute manipulation de données localisées. Cependant on constate que les systèmes de référence et de coordonnées sont aujourd hui très souvent traités de façon insuffisamment complète et précise dans les logiciels SIG. L étude conduit à développer un outil interactif et éducatif, dédié aux utilisateurs SIG. Cet outil est destiné à traiter des données matricielles et vectorielles. Son interface homme-machine guide l utilisateur dans ses choix. En illustration et validation de ce travail, est abordé le cas pratique du Liban qui a été confronté aux problèmes de passage vers le nouveau système créé en utilisant le système GPS. On présente les différentes possibilités pour ce passage ainsi que la grille de transformation planimétrique calculéePARIS-EST Marne-la-Vallee-BU (774682101) / SudocSudocFranceF

INTEGRATING AND MANAGING BIM IN GIS, SOFTWARE REVIEW

International audienc

Automatic Reconstruction of 3D Building Models from Terrestrial Laser Scanner Data

With modern 3D laser scanners we can acquire a large amount of 3D data in only a few minutes. This technology results in a growing number of applications ranging from the digitalization of historical artifacts to facial authentication. The modeling process demands a lot of time and work (Tim Volodine, 2007). In comparison with the other two stages, the acquisition and the registration, the degree of automation of the modeling stage is almost zero. In this paper, we propose a new surface reconstruction technique for buildings to process the data obtained by a 3D laser scanner. These data are called a point cloud which is a collection of points sampled from the surface of a 3D object. Such a point cloud can consist of millions of points. In order to work more efficiently, we worked with simplified models which contain less points and so less details than a point cloud obtained in situ. The goal of this study was to facilitate the modeling process of a building starting from 3D laser scanner data. In order to do this, we wrote two scripts for Rhinoceros 5.0 based on intelligent algorithms. The first script finds the exterior outline of a building. With a minimum of human interaction, there is a thin box drawn around the surface of a wall. This box is able to rotate 360° around an axis in a corner of the wall in search for the points of other walls. In this way we can eliminate noise points. These are unwanted or irrelevant points. If there is an angled roof, the box can also turn around the edge of the wall and the roof. With the different positions of the box we can calculate the exterior outline. The second script draws the interior outline in a surface of a building. By interior outline we mean the outline of the openings like windows or doors. This script is based on the distances between the points and vector characteristics. Two consecutive points with a relative big distance will form the outline of an opening. Once those points are found, the interior outline can be drawn. The designed scripts are able to ensure for simple point clouds: the elimination of almost all noise points and the reconstruction of a CAD model