Phage-Mediated Acquisition of a Type III Secreted Effector Protein Boosts Growth of Salmonella by Nitrate Respiration

Information on how emerging pathogens can invade and persist and spread within host populations remains sparse. In the 1980s, a multidrug-resistant Salmonella enterica serotype Typhimurium clone lysogenized by a bacteriophage carrying the sopE virulence gene caused an epidemic among cattle and humans in Europe. Here we show that phage-mediated horizontal transfer of the sopE gene enhances the production of host-derived nitrate, an energetically highly valuable electron acceptor, in a mouse colitis model. In turn, nitrate fuels a bloom of S. Typhimurium in the gut lumen through anaerobic nitrate respiration while suppressing genes for the utilization of energetically inferior electron acceptors such as tetrathionate. Through this mechanism, horizontal transfer of sopE can enhance the fitness of S. Typhimurium, resulting in its significantly increased abundance in the feces

Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings.

An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa.This work was supported by the Wellcome Trust. We would like to thank the members of the Pathogen Informatics Team and the core sequencing teams at the Wellcome Trust Sanger Institute (Cambridge, UK). We are grateful to D. Harris for work in managing the sequence data

Symbiodiniaceae diversity and characterization of palytoxin in various zoantharians (Anthozoa, Hexacorallia)

International audienceAnemone-like animals belonging to the order Zoantharia are common anthozoans widely distributed from shallow to deep tropical and subtropical waters. Some species are well-known because of their high toxicity due to the presence of palytoxin (PLTX) in their tissues. PLTX is a large polyhydroxylated compound and one of the most potent toxins known. Currently, the PLTX biosynthetic pathway in zoantharians and the role of the host or the putative symbiotic organism(s) involved in this pathway are entirely unknown. To better understand the presence of PLTX in some Zoantharia, twenty-nine zoantharian colonies were analysed in this study. All zoantharian samples and their endosymbiotic dinoflagellates (Symbiodiniaceae = Zooxanthellae) were identified using DNA barcoding and phylogenetic reconstructions. Quantification of PLTX and its analogues showed that the yields contained in Palythoa heliodiscus, Palythoa aff. clavata and one potentially undescribed species of Palythoa are among the highest ever found (up to > 2 mg/g of wet zoantharian). Mass spectrometry imaging was used for the first time on Palythoa samples and revealed that in situ distribution of PLTX is mainly located in ectodermal tissues such as the epidermis of the body wall and the pharynx. Moreover, high levels of PLTX have been detected in histological regions where few or no Symbiodiniaceae cells could be observed. Finally, issues such as host-specificity and environmental variables driving biogeographical patterns of hosted Symbiodiniaceae in zoantharian lineages were discussed in light of our phylogenetic results as well as the patterns of PLTX distribution. It was concluded that (1) the variability of Symbiodiniaceae diversity may be related to ecological divergence in Zoantharia, (2) All Palythoa species hosted Cladocopium Symbiodiniaceae (formerly clade C), (3) the sole presence of Cladocopium is not sufficient to explain the presence of high concentrations of PLTX and/or its analogues and (4) the ability to produce high levels of PLTX and/or its analogues highlighted in some Palythoa species could be a plesiomorphic character inherited from their last common ancestor and subsequently lost in several lineages

Renin – angiotensin system and cardiometabolic risk

En años recientes el concepto clásico del sistema renina angiotensina ha experimentado cambios sustanciales. La identificación de los nuevos componentes del sistema renina angiotensina ha contribuido a modificar nuestro entendimiento acerca de su función en condiciones fisiológicas así como en diversas enfermedades. En este artículo de revisión nos enfocaremos en el papel de este sistema endocrino en el riesgo cardiometabólico.3-10In the past few years the classical concept of the renin-angiotensin system has experienced substantial changes. The identification of the new components of the renin-angiotensin system have contributed to switch our understanding about its function in physiological situations and in several diseases. In this review we will focus on the role of this endocrine system in the cardiometabolic risk

A Low Molecular Weight Protein from the Sea Anemone Anemonia viridis with an Anti-Angiogenic Activity

Sea anemones are a remarkable source of active principles due to a decentralized venom system. New blood vessel growth or angiogenesis is a very promising target against cancer, but the few available antiangiogenic compounds have limited efficacy. In this study, a protein fraction, purified from tentacles of Anemonia viridis, was able to limit endothelial cells proliferation and angiogenesis at low concentration (14 nM). Protein sequences were determined with Edman degradation and mass spectrometry in source decay and revealed homologies with Blood Depressing Substance (BDS) sea anemones. The presence of a two-turn alpha helix observed with circular dichroism and a trypsin activity inhibition suggested that the active principle could be a Kunitz-type inhibitor, which may interact with an integrin due to an Arginine Glycin Aspartate (RGD) motif. Molecular modeling showed that this RGD motif was well exposed to solvent. This active principle could improve antiangiogenic therapy from existing antiangiogenic compounds binding on the Vascular Endothelial Growth Factor (VEGF)

Improvement of mosquito identification by MALDI-TOF MS biotyping using protein signatures from two body parts

Abstract Background Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology (MALDI-TOF MS) is an innovative tool that has been shown to be effective for the identification of numerous arthropod groups including mosquitoes. A critical step in the implementation of MALDI-TOF MS identification is the creation of spectra databases (DB) for the species of interest. Mosquito legs were the body part most frequently used to create identification DB. However, legs are one of the most fragile mosquito compartments, which can put identification at risk. Here, we assessed whether mosquito thoraxes could also be used as a relevant body part for mosquito species identification using a MALDI-TOF MS biotyping strategy; we propose a double DB query strategy to reinforce identification success. Methods Thoraxes and legs from 91 mosquito specimens belonging to seven mosquito species collected in six localities from Guadeloupe, and two laboratory strains, Aedes aegypti BORA and Aedes albopictus Marseille, were dissected and analyzed by MALDI-TOF MS. Molecular identification using cox1 gene sequencing was also conducted on representative specimens to confirm their identification. Results MS profiles obtained with both thoraxes and legs were highly compartment-specific, species-specific and species-reproducible, allowing high identification scores (log-score values, LSVs) when queried against the in-house MS reference spectra DB (thorax LSVs range: 2.260–2.783, leg LSVs range: 2.132–2.753). Conclusions Both thoraxes and legs could be used for a double DB query in order to reinforce the success and accuracy of MALDI-TOF MS identification

Phage-mediated acquisition of a type III secreted effector protein boosts growth of salmonella by nitrate respiration.

Information on how emerging pathogens can invade and persist and spread within host populations remains sparse. In the 1980s, a multidrug-resistant Salmonella enterica serotype Typhimurium clone lysogenized by a bacteriophage carrying the sopE virulence gene caused an epidemic among cattle and humans in Europe. Here we show that phage-mediated horizontal transfer of the sopE gene enhances the production of host-derived nitrate, an energetically highly valuable electron acceptor, in a mouse colitis model. In turn, nitrate fuels a bloom of S. Typhimurium in the gut lumen through anaerobic nitrate respiration while suppressing genes for the utilization of energetically inferior electron acceptors such as tetrathionate. Through this mechanism, horizontal transfer of sopE can enhance the fitness of S. Typhimurium, resulting in its significantly increased abundance in the feces. IMPORTANCE During gastroenteritis, Salmonella enterica serotype Typhimurium can use tetrathionate respiration to edge out competing microbes in the gut lumen. However, the concept that tetrathionate respiration confers a growth benefit in the inflamed gut is not broadly applicable to other host-pathogen combinations because tetrathionate respiration is a signature trait used to differentiate Salmonella serotypes from most other members of the family Enterobacteriaceae. Here we show that by acquiring the phage-carried sopE gene, S. Typhimurium can drive the host to generate an additional respiratory electron acceptor, nitrate. Nitrate suppresses genes for the utilization of energetically inferior electron acceptors such as tetrathionate while enhancing the luminal growth of S. Typhimurium through anaerobic nitrate respiration. Pathways for anaerobic nitrate respiration are widely conserved among members of the family Enterobacteriaceae, thereby making our observations relevant to other enteric pathogens whose relative abundance in the intestinal lumen increases during infection

Inhibitor of Apoptosis Proteins Determine Glioblastoma Stem-Like Cells Fate in an Oxygen-Dependent Manner

International audienceIn glioblastomas, apoptosis inhibitor proteins (IAPs) are involved in apoptotic and non-apoptotic processes. We previously showed that IAPs inhibition induced a loss of stemness and glioblastoma stem cells differentiation by activating nuclear factor-κB under normoxic conditions. Hypoxia has been shown to modulate drug efficacy. Here, we investigated how IAPs participate in glioblastoma stem-like cell maintenance and fate under hypoxia. We showed that in a hypoxic environment, IAPs inhibition by GDC-0152, a small-molecule IAPs inhibitor, triggered stem-like cell apoptosis and decreased proliferation in four human glioblastoma cell lines. We set up a three-dimensional glioblastoma spheroid model in which time-of-flight secondary ion mass spectrometry analyses revealed a decrease in oxygen levels between the periphery and core. We observed low proliferative and apoptotic cells located close to the hypoxic core of the spheres and glial fibrillary acidic protein+ cells at their periphery. These oxygen-dependent GDC-0152 antitumoral effects have been confirmed on human glioblastoma explants. Notably, serine-threonine kinase activation analysis revealed that under hypoxic conditions, IAPs inhibition activated ataxia telangiectasia and Rad3-related protein signaling. Our findings provide new insights into the dual mechanism of action of IAPs inhibitors that depends on oxygen level and are relevant to their therapeutic application in tumors. Stem Cells 2019

NATURAL GAS RESOURCES IN DEEP SEDIMENTARY BASINS

From a geological perspective, deep natural gas resources are generally defined as resources occurring in reservoirs at or below 15,000 feet, whereas ultra-deep gas occurs below 25,000 feet. From an operational point of view, ''deep'' is often thought of in a relative sense based on the geologic and engineering knowledge of gas (and oil) resources in a particular area. Deep gas can be found in either conventionally-trapped or unconventional basin-center accumulations that are essentially large single fields having spatial dimensions often exceeding those of conventional fields. Exploration for deep conventional and unconventional basin-center natural gas resources deserves special attention because these resources are widespread and occur in diverse geologic environments. In 1995, the U.S. Geological Survey estimated that 939 TCF of technically recoverable natural gas remained to be discovered or was part of reserve appreciation from known fields in the onshore areas and State waters of the United. Of this USGS resource, nearly 114 trillion cubic feet (Tcf) of technically-recoverable gas remains to be discovered from deep sedimentary basins. Worldwide estimates of deep gas are also high. The U.S. Geological Survey World Petroleum Assessment 2000 Project recently estimated a world mean undiscovered conventional gas resource outside the U.S. of 844 Tcf below 4.5 km (about 15,000 feet). Less is known about the origins of deep gas than about the origins of gas at shallower depths because fewer wells have been drilled into the deeper portions of many basins. Some of the many factors contributing to the origin of deep gas include the thermal stability of methane, the role of water and non-hydrocarbon gases in natural gas generation, porosity loss with increasing thermal maturity, the kinetics of deep gas generation, thermal cracking of oil to gas, and source rock potential based on thermal maturity and kerogen type. Recent experimental simulations using laboratory pyrolysis methods have provided much information on the origins of deep gas. Technologic problems are one of the greatest challenges to deep drilling. Problems associated with overcoming hostile drilling environments (e.g. high temperatures and pressures, and acid gases such as CO{sub 2} and H{sub 2}S) for successful well completion, present the greatest obstacles to drilling, evaluating, and developing deep gas fields. Even though the overall success ratio for deep wells is about 50 percent, a lack of geological and geophysical information such as reservoir quality, trap development, and gas composition continues to be a major barrier to deep gas exploration. Results of recent finding-cost studies by depth interval for the onshore U.S. indicate that, on average, deep wells cost nearly 10 times more to drill than shallow wells, but well costs and gas recoveries vary widely among different gas plays in different basins. Based on an analysis of natural gas assessments, many topical areas hold significant promise for future exploration and development. One such area involves re-evaluating and assessing hypothetical unconventional basin-center gas plays. Poorly-understood basin-center gas plays could contain significant deep undiscovered technically-recoverable gas resources