Cancer cells in acidic tumor regions are aggressive and a key therapeutic target, but distinguishing between acid-exposed and hypoxic cells is challenging. Here, we use carbonic anhydrase 9 (CA9) antibodies to mark acidic areas in both hypoxic and respiring tumor areas, along with an HRE-GFP reporter for hypoxia, to isolate distinct cell populations from 3D tumor spheroids. Transcriptomic analysis of CA9-positive, hypoxia-negative cells highlights enriched fatty acid desaturase activity.
View Article and Find Full Text PDFBackground: Immunogenic cell death (ICD) and ferroptosis have recently emerged as key factors in the anticancer immune response. Among the treatments able to induce ICD and the associated release of danger signals is photodynamic therapy (PDT). Ferroptosis for its part results from lipid peroxidation and is induced by CD8 T cells to kill nearby cancer cells on IFN-γ production.
View Article and Find Full Text PDFExtracellular vesicles (EVs) are mediators of intercellular communication in the tumor microenvironment. Tumor EVs are commonly associated with metastasis, immunosuppression or drug resistance. Viral infections usually increase EV secretion, but little is known about the effect of oncolytic viruses (OVs) on tumor EVs.
View Article and Find Full Text PDFTumor acidosis is associated with increased invasiveness and drug resistance. Here, we take an unbiased approach to identify vulnerabilities of acid-exposed cancer cells by combining pH-dependent flow cytometry cell sorting from 3D colorectal tumor spheroids and transcriptomic profiling. Besides metabolic rewiring, we identify an increase in tetraploid cell frequency and DNA damage response as consistent hallmarks of acid-exposed cancer cells, supported by the activation of ATM and ATR signaling pathways.
View Article and Find Full Text PDFHere we report, for the first time, the occurrence of the bacteria from the species complex in Iceland. We isolated this bacterium from 35 of the 38 samples of angiosperms, moss, ferns and leaf litter collected across the island from five habitat categories (boreal heath, forest, subalpine and glacial scrub, grazed pasture, lava field). The culturable populations of on these plants varied in size across 6 orders of magnitude, were as dense as 10 cfu g and were composed of strains in phylogroups 1, 2, 4, 6, 7, 10 and 13.
View Article and Find Full Text PDFTumor acidosis promotes disease progression through a stimulation of fatty acid (FA) metabolism in cancer cells. Instead of blocking the use of FAs by acidic cancer cells, we examined whether excess uptake of specific FAs could lead to antitumor effects. We found that n-3 but also remarkably n-6 polyunsaturated FA (PUFA) selectively induced ferroptosis in cancer cells under ambient acidosis.
View Article and Find Full Text PDFMetabolic plasticity in cancer cells makes use of metabolism-targeting agents very challenging. Drug-induced metabolic rewiring may, however, uncover vulnerabilities that can be exploited. We report that resistance to glycolysis inhibitor 3-bromopyruvate (3-BrPA) arises from DNA methylation in treated cancer cells and subsequent silencing of the monocarboxylate transporter MCT1.
View Article and Find Full Text PDFAcidosis, a common characteristic of the tumor microenvironment, is associated with alterations in metabolic preferences of cancer cells and progression of the disease. Here we identify the TGF-β2 isoform at the interface between these observations. We document that acidic pH promotes autocrine TGF-β2 signaling, which in turn favors the formation of lipid droplets (LD) that represent energy stores readily available to support anoikis resistance and cancer cell invasiveness.
View Article and Find Full Text PDFDecreased reliance on pesticides can be achieved through a clever use of eco-evolutionary knowledge via intercropping economically valuable crops with companion plants that can hamper pest outbreaks. We created a greenhouse multi-layered microcosm system to test two potato peach aphid clones, performing alone or in competition, on mixes of genetically variable cultivars of cabbage, with and without onion. The onion acted as a nuisance/disturbance for the pest, which was generally for the benefit of the cabbage albeit both plants sharing space and nutrients.
View Article and Find Full Text PDFThe cardiopathogenic role of autoantibodies (aabs) directed against β1-adrenoreceptors (β1-AR) is well established. In mouse models, they cause progressive dilated cardiomyopathy (DCM) whose characterization with echocardiography requires prolonged protocols with numerous animals, complicating the evaluation of new treatments. Here, we report on the characterization of β1-aabs-induced DCM in mice using 11.
View Article and Find Full Text PDFAims: The aim of this study was to develop a rapid PCR-based method for the specific detection of individual phylogroups of the Pseudomonas syringae complex.
Methods And Results: Seven primer pairs were developed by analysing whole genomes of 54 Ps. syringae strains.
We present a reliable PCR-based method to avoid the biases related to identification based on the conventional phenotypes currently used in the identification of Pseudomonas syringae sensu lato, a ubiquitous environmental bacterium including plant pathogens. We identified a DNA target suitable for this purpose by applying a comparative genomic pipeline to Pseudomonas genomes. We designed primers and developed PCR conditions that led to a clean and strong PCR product from 97% of the 185 strains of P.
View Article and Find Full Text PDFFlowering time in annual plants has large fitness consequences and has been the focus of theoretical and empirical study. Previous theory has concluded that flowering time has evolved over evolutionary time to maximize fitness over a particular season length. We introduce a new model where flowering is cued by a growth-rate rule (peak nitrogen (N)).
View Article and Find Full Text PDFThe Pseudomonas syringae complex is composed of numerous genetic lineages of strains from both agricultural and environmental habitats including habitats closely linked to the water cycle. The new insights from the discovery of this bacterial species in habitats outside of agricultural contexts per se have led to the revelation of a wide diversity of strains in this complex beyond what was known from agricultural contexts. Here, through Multi Locus Sequence Typing (MLST) of 216 strains, we identified 23 clades within 13 phylogroups among which the seven previously described P.
View Article and Find Full Text PDFNew economically important diseases on crops and forest trees emerge recurrently. An understanding of where new pathogenic lines come from and how they evolve is fundamental for the deployment of accurate surveillance methods. We used kiwifruit bacterial canker as a model to assess the importance of potential reservoirs of new pathogenic lineages.
View Article and Find Full Text PDFAs a species complex, Pseudomonas syringae exists in both agriculture and natural aquatic habitats. P.viridiflava, a member of this complex, has been reported to be phenotypically largely homogenous.
View Article and Find Full Text PDFHere, we report the draft genome sequences for 7 phylogenetically diverse isolates of Pseudomonas syringae, obtained from numerous environmental sources and geographically proximate crop species. Overall, these sequences provide a wealth of information about the differences (or lack thereof) between isolates from disease outbreaks and those from other sources.
View Article and Find Full Text PDFThe type III secretion system (T3SS) is an important virulence factor of pathogenic bacteria, but the natural occurrence of variants of bacterial plant pathogens with deficiencies in their T3SS raises questions about the significance of the T3SS for fitness. Previous work on T3SS-deficient plant pathogenic bacteria has focused on strains from plants or plant debris. Here we have characterized T3SS-deficient strains of Pseudomonas syringae from plant and nonplant substrates in pristine nonagricultural contexts, many of which represent recently described clades not yet found associated with crop plants.
View Article and Find Full Text PDFThe recently discovered ubiquity of the plant pathogen Pseudomonas syringae in headwaters and alpine ecosystems worldwide elicits new questions about the ecology of this bacterium and subsequent consequences for disease epidemiology. Because of the major contribution of snow to river run-off during crop growth, we evaluated the population dynamics of P.syringae in snowpack and the underlying leaf litter during two years in the Southern French Alps.
View Article and Find Full Text PDFNonhost environmental reservoirs of pathogens play key roles in their evolutionary ecology and in particular in the evolution of pathogenicity. In light of recent reports of the plant pathogen Pseudomonas syringae in pristine waters outside agricultural regions and its dissemination via the water cycle, we have examined the genetic and phenotypic diversity, population structure, and biogeography of P. syringae from headwaters of rivers on three continents and their phylogenetic relationship to strains from crops.
View Article and Find Full Text PDFEarly detection of tumor-specific autoantibodies (auto-Abs) has the potential to be used for cancer screening and diagnosis. Whether auto-Ab may be useful to track metastatic progression or response to treatment is, however, largely unknown. To address these issues, the serological proteome was analyzed in an invasive but treatment-responsive mouse tumor model.
View Article and Find Full Text PDFIn 2005, an extensive survey of bacterial wilt in Cameroon collected 110 strains of Ralstonia solanacearum from wilting tomato, potato, pepper, huckleberry (Solanum scabrum), sesame, and amaranth. The genetic diversity and phylogeny of selected strains from Cameroon were assessed by multiplex-polymerase chain reaction (PCR), race 3/biovar 2-specific PCR, and sequence analyses of the mutS and egl genes. These data were compared with those from 33 reference strains covering the known diversity within the R.
View Article and Find Full Text PDFPseudomonas syringae is a plant pathogen well known for its capacity to grow epiphytically on diverse plants and for its ice-nucleation activity. The ensemble of its known biology and ecology led us to postulate that this bacterium is also present in non-agricultural habitats, particularly those associated with water. Here, we report the abundance of P.
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