The Enteropathogenic E. coli (EPEC) Tir Effector Inhibits NF-κB Activity by Targeting TNFα Receptor-Associated Factors

Enteropathogenic Escherichia coli (EPEC) disease depends on the transfer of effector proteins into epithelia lining the human small intestine. EPEC E2348/69 has at least 20 effector genes of which six are located with the effector-delivery system genes on the Locus of Enterocyte Effacement (LEE) Pathogenicity Island. Our previous work implied that non-LEE-encoded (Nle) effectors possess functions that inhibit epithelial anti-microbial and inflammation-inducing responses by blocking NF-κB transcription factor activity. Indeed, screens by us and others have identified novel inhibitory mechanisms for NleC and NleH, with key co-operative functions for NleB1 and NleE1. Here, we demonstrate that the LEE-encoded Translocated-intimin receptor (Tir) effector has a potent and specific ability to inhibit NF-κB activation. Indeed, biochemical, imaging and immunoprecipitation studies reveal a novel inhibitory mechanism whereby Tir interaction with cytoplasm-located TNFα receptor-associated factor (TRAF) adaptor proteins induces their proteasomal-independent degradation. Infection studies support this Tir-TRAF relationship but reveal that Tir, like NleC and NleH, has a non-essential contribution in EPEC's NF-κB inhibitory capacity linked to Tir's activity being suppressed by undefined EPEC factors. Infections in a disease-relevant intestinal model confirm key NF-κB inhibitory roles for the NleB1/NleE1 effectors, with other studies providing insights on host targets. The work not only reveals a second Intimin-independent property for Tir and a novel EPEC effector-mediated NF-κB inhibitory mechanism but also lends itself to speculations on the evolution of EPEC's capacity to inhibit NF-κB function

The Interplay between Entamoeba and Enteropathogenic Bacteria Modulates Epithelial Cell Damage

In amoebiasis, a human disease that is a serious health problem in many developing countries, efforts have been made to identify responsible factors for the tissue damage inflicted by the parasite Entamoeba histolytica. This amoeba lives in the lumen of the colon without causing damage to the intestinal mucosa, but under unknown circumstances becomes invasive, destroying the intestinal tissue. Bacteria in the intestinal flora have been proposed as inducers of higher amoebic virulence, but the causes or mechanisms responsible for the induction are still undetermined. Mixed intestinal infections with Entamoeba histolytica and enteropathogenic bacteria, showing exacerbated manifestations of disease, are common in endemic countries. We implemented an experimental system to study amoebic virulence in the presence of pathogenic bacteria and its consequences on epithelial cells. Results showed that amoebae that ingested enteropathogenic bacteria became more virulent, causing more damage to epithelial cells. Bacteria induced release of inflammatory proteins by the epithelial cells that attracted amoebae, facilitating amoebic contact to the epithelial cells and higher damage. Our results, although a first approach to this complex problem, provide insights into amoebic infections, as interplay with other pathogens apparently influences the intestinal environment, the behavior of cells involved and the manifestations of the disease

Formation of supercontinents linked to increases in atmospheric oxygen

Atmospheric oxygen concentrations in the Earth’s atmosphere rose from negligible levels in the Archaean Era to about 21% in the present day. This increase is thought to have occurred in six steps, 2.65, 2.45, 1.8, 0.6, 0.3 and 0.04 billion years ago, with a possible seventh event identified at 1.2 billion years ago. Here we show that the timing of these steps correlates with the amalgamation of Earth’s land masses into supercontinents. We suggest that the continent–continent collisions required to form supercontinents produced supermountains. In our scenario, these supermountains eroded quickly and released large amounts of nutrients such as iron and phosphorus into the oceans, leading to an explosion of algae and cyanobacteria, and thus a marked increase in photosynthesis, and the photosynthetic production of O2. Enhanced sedimentation during these periods promoted the burial of a high fraction of organic carbon and pyrite, thus preventing their reaction with free oxygen, and leading to sustained increases in atmospheric oxygen

Two-step rise of atmospheric oxygen linked to the growth of continents

© 2016 Macmillan Publishers Limited.Earth owes its oxygenated atmosphere to its unique claim on life, but how the atmosphere evolved from an initially oxygen-free state remains unresolved. The rise of atmospheric oxygen occurred in two stages: approximately 2.5 to 2.0 billion years ago during the Great Oxidation Event and roughly 2 billion years later during the Neoproterozoic Oxygenation Event. We propose that the formation of continents about 2.7 to 2.5 billion years ago, perhaps due to the initiation of plate tectonics, may have led to oxygenation by the following mechanisms. In the first stage, the change in composition of Earth's crust from iron- and magnesium-rich mafic rocks to feldspar- and quartz-rich felsic rocks could have caused a decrease in the oxidative efficiency of the Earth's surface, allowing atmospheric O2 to rise. Over the next billion years, as carbon steadily accumulated on the continents, metamorphic and magmatic reactions within this growing continental carbon reservoir facilitated a gradual increase in the total long-term input of CO2 to the ocean-atmosphere system. Given that O2 is produced during organic carbon burial, the increased CO2 input may have triggered a second rise in O2. A two-step rise in atmospheric O2 may therefore be a natural consequence of plate tectonics, continent formation and the growth of a crustal carbon reservoir.Link_to_subscribed_fulltex

Petrology, bulk-rock geochemistry, indicator mineral composition and zircon U–Pb geochronology of the end-cretaceous diamondiferous mainpur orangeites, Bastar Craton, Central India

The end-Cretaceous diamondiferous Mainpur orangeite field comprises six pipes (Behradih, Kodomali, Payalikhand, Jangara, Kosambura and Bajaghati) located at the NE margin of the Bastar craton, central India. The preservation of both diatreme (Behradih) and hypabyssal facies (Kodomali) in this domain implies differential erosion. The Behradih samples are pelletal and tuffisitic in their textural habit, whereas those of the Kodomali pipe have inequigranular texture and comprise aggregates of two generations of relatively fresh olivines. The Kosambura pipe displays high degrees of alteration and contamination with silicified macrocrysts and carbonated groundmass. Olivine, spinel and clinopyroxene in the Behradih and the Kodomali pipes share overlapping compositions, whereas the groundmass phlogopite and perovskite show conspicuous compositional differences. The bulk-rock geochemistry of both the Behradih and Kodomali pipes has a more fractionated nature compared to southern African orangeites. Incompatible trace elements and their ratios readily distinguish them from the Mesoproterozoic Wajrakarur (WKF) and the Narayanpet kimberlites (NKF) from the eastern Dharwar craton, southern India, and bring out their similarity in petrogenesis to southern African orangeites. The pyrope population in the Mainpur orangeites is dominated by the calcic-lherzolitic variety, with sub-calcic harzburgitic and eclogitic garnets in far lesser proportion. Garnet REE distribution patterns from the Behradih and Payalikhand pipes display “smooth” as well as “sinusoidal” chondrite-normalised patterns. They provide evidence for the presence of a compositionally layered end-Cretaceous sub-Bastar craton mantle, similar to that reported from many other cratons worldwide. The high logfO₂ of the Mainpur orangeite magma (ΔNNO (nickel-nickel oxide) of +0.48 to +4.46 indicates that the redox state of the lithospheric mantle cannot be of first-order control for diamond potential and highlights the dominant role of other factors such as rapid magma transport. The highly diamondiferous nature, the abundance of calcic-lherzolitic garnets and highly oxidising conditions prevailing at the time of eruption make the Mainpur orangeites clearly “anomalous” compared to several other kimberlite pipes worldwide. U–Pb dating of zircon xenocrysts from the Behradih pipe yielded distinct Palaeoproterozoic ages with a predominant age around 2,450 Ma. The lack of Archean-aged zircons, in spite of the fact that the Bastar craton is the oldest continental nuclei in the Indian shield with an Eoarchaean crust of 3.5–3.6 Ga, could either be a reflection of the sampling process or of the modification of the sub-Bastar lithosphere by the invading Deccan plume-derived melts during the Late Cretaceous