The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD.

Mycobacterium tuberculosis (Mtb) induces necrosis of infected cells to evade immune responses. Recently, we found that Mtb uses the protein CpnT to kill human macrophages by secreting its C-terminal domain, named tuberculosis necrotizing toxin (TNT), which induces necrosis by an unknown mechanism. Here we show that TNT gains access to the cytosol of Mtb-infected macrophages, where it hydrolyzes the essential coenzyme NAD(+). Expression or injection of a noncatalytic TNT mutant showed no cytotoxicity in macrophages or in zebrafish zygotes, respectively, thus demonstrating that the NAD(+) glycohydrolase activity is required for TNT-induced cell death. To prevent self-poisoning, Mtb produces an immunity factor for TNT (IFT) that binds TNT and inhibits its activity. The crystal structure of the TNT-IFT complex revealed a new NAD(+) glycohydrolase fold of TNT, the founding member of a toxin family widespread in pathogenic microorganisms

Colossians

The Apostle Paul’s Letter to the Colossians offers a valuable and intimate glimpse into the life of a fledgling Christian community as it struggled to define Christian doctrine and theology. Paul was prompted to write to the Colossian assembly when he heard that “false teachers” had joined the congregation and were advocating dangerous, non-Christian practices. In an effort to appear superior, these heretical teachers were luring Christians to exercise asceticism, moral rigorism, and esoteric rituals―hallmarks of other “mystery” and pagan cults. In his passionate letter, Paul denounces these extreme and elitist practices and firmly defends a life in Christ. He proclaims that pure, simple worship of Christ alone is the most powerful statement of faith. In their astute and lucid commentary, eminent New Testament scholars Markus Barth and Helmut Blanke re-create the turbulent age of the birth of Christianity and examine the myriad “outside” influences―from cold, rational Hellenistic philosophy to exclusive, ethereal Gnostic thought―that often threatened the evolution of Christian theology. Colossians not only provides a new and carefully balanced analysis of this pivotal New Testament text but also chronicles the development of Christian thought as it gradually spread throughout the Roman Empire.</JATS1:p

Identification of the Cellular Receptor of Clostridium spiroforme Toxin

Clostridium spiroforme produces the binary actin-ADP-ribosylating toxin CST (C. spiroforme toxin), which has been proposed to be responsible for diarrhea, enterocolitis, and eventually death, especially in rabbits. Here we report on the recombinant production of the enzyme component (CSTa) and the binding component (CSTb) of C. spiroforme toxin in Bacillus megaterium. By using the recombinant toxin components, we show that CST enters target cells via the lipolysis-stimulated lipoprotein receptor (LSR), which has been recently identified as the host cell receptor of the binary toxins Clostridium difficile transferase (CDT) and Clostridium perfringens iota toxin. Microscopic studies revealed that CST, but not the related Clostridium botulinum C2 toxin, colocalized with LSR during toxin uptake and traffic to endosomal compartments. Our findings indicate that CST shares LSR with C. difficile CDT and C. perfringens iota toxin as a host cell surface receptor

On the role of the mesoscale circulation on an idealized coastal upwelling ecosystem

International audienceAn idealized circulation model of coastal upwelling coupled to an ecosystem model has been built to address the impact of features such as eddies and filaments emerging from mesoscale dynamics on a marine ecosystem. The model mimics coastal upwelling along an infinite straight coast with north-south cyclic boundary conditions. Thanks to the parametrization of the geostrophic onshore flow in the thermocline, the circulation captures the typical characteristics of a coastal upwelling region: an equatorward coastal jet, a poleward undercurrent along the continental slope and mesoscale eddies and filaments. This eddying three-dimensional simulation is compared to a two-dimensional simulation using the averaged velocity field of the first simulation as velocity field. This approach allows us to compare simulations having similar upwelling and nutrient input but differing in the nature of the flow. An offshore spreading of the phytoplankton bloom is found in the eddying simulation. The width of the productive coastal band is increased from 80 km to 200 km by the mesoscale activity. A biogeochemical budget carried out in a 300 km-wide coastal band provides evidence that mesoscale activity decreases the total phytoplankton content mainly by exporting a significant part of the surface phytoplankton below the euphotic layer. In presence of mesoscale activity, the downward and offshore export of phytoplankton, zooplankton and detritus significantly contributes to total export of organic matter out of the surface coastal ocean, whereas their contribution to export is weak in the two-dimensional case