28 research outputs found
A modularity based spectral method for simultaneous community and anti-community detection
In a graph or complex network, communities and anti-communities are node sets
whose modularity attains extremely large values, positive and negative,
respectively. We consider the simultaneous detection of communities and
anti-communities, by looking at spectral methods based on various matrix-based
definitions of the modularity of a vertex set. Invariant subspaces associated
to extreme eigenvalues of these matrices provide indications on the presence of
both kinds of modular structure in the network. The localization of the
relevant invariant subspaces can be estimated by looking at particular matrix
angles based on Frobenius inner products
Iron acquisition in Bacillus cereus: the roles of IlsA and bacillibactin in exogenous ferritin iron mobilization
9siIn host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A) binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis.openopenSegond D; Abi Khalil E; Buisson C; Daou N; Kallassy M; Lereclus D; Arosio P; Bou-Abdallah F; Nielsen Le Roux C.Segond, D; Abi Khalil, E; Buisson, C; Daou, N; Kallassy, M; Lereclus, D; Arosio, Paolo; Bou Abdallah, F; Nielsen Le Roux, C
IlsA, A Unique Surface Protein of Bacillus cereus Required for Iron Acquisition from Heme, Hemoglobin and Ferritin
The human opportunistic pathogen Bacillus cereus belongs to the B. cereus group that includes bacteria with a broad host spectrum. The ability of these bacteria to colonize diverse hosts is reliant on the presence of adaptation factors. Previously, an IVET strategy led to the identification of a novel B. cereus protein (IlsA, Iron-regulated leucine rich surface protein), which is specifically expressed in the insect host or under iron restrictive conditions in vitro. Here, we show that IlsA is localized on the surface of B. cereus and hence has the potential to interact with host proteins. We report that B. cereus uses hemoglobin, heme and ferritin, but not transferrin and lactoferrin. In addition, affinity tests revealed that IlsA interacts with both hemoglobin and ferritin. Furthermore, IlsA directly binds heme probably through the NEAT domain. Inactivation of ilsA drastically decreases the ability of B. cereus to grow in the presence of hemoglobin, heme and ferritin, indicating that IlsA is essential for iron acquisition from these iron sources. In addition, the ilsA mutant displays a reduction in growth and virulence in an insect model. Hence, our results indicate that IlsA is a key factor within a new iron acquisition system, playing an important role in the general virulence strategy adapted by B. cereus to colonize susceptible hosts
The quasi-universality of nestedness in the structure of quantitative plant-parasite interactions
Understanding the relationships between host range and pathogenicity for parasites, and between the efficiency and scope of immunity for hosts are essential to implement efficient disease control strategies. In the case of plant parasites, most studies have focused on describing qualitative interactions and a variety of genetic and evolutionary models has been proposed in this context. Although plant quantitative resistance benefits from advantages in terms of durability, we presently lack models that account for quantitative interactions between plants and their parasites and the evolution of these interactions. Nestedness and modularity are important features to unravel the overall structure of host-parasite interaction matrices. Here, we analysed these two features on 32 matrices of quantitative pathogenicity trait data gathered from 15 plant-parasite pathosystems consisting of either annual or perennial plants along with fungi or oomycetes, bacteria, nematodes, insects and viruses. The performance of several nestedness and modularity algorithms was evaluated through a simulation approach, which helped interpretation of the results. We observed significant modularity in only six of the 32 matrices, with two or three modules detected. For three of these matrices, modules could be related to resistance quantitative trait loci present in the host. In contrast, we found high and significant nestedness in 30 of the 32 matrices. Nestedness was linked to other properties of plant-parasite interactions. First, pathogenicity trait values were explained in majority by a parasite strain effect and a plant accession effect, with no parasite-plant interaction term. Second, correlations between the efficiency and scope of the resistance of plant genotypes, and between the host range breadth and pathogenicity level of parasite strains were overall positive. This latter result questions the efficiency of strategies based on the deployment of several genetically-differentiated cultivars of a given crop species in the case of quantitative plant immunity
Astrocyte-neuron interplay is critical for Alzheimer's disease pathogenesis and is rescued by TRPA1 channel blockade
International audienceAbstract The sequence of cellular dysfunctions in preclinical Alzheimerâs disease must be understood if we are to plot new therapeutic routes. Hippocampal neuronal hyperactivity is one of the earliest events occurring during the preclinical stages of Alzheimerâs disease in both humans and mouse models. The most common hypothesis describes amyloid-ÎČ accumulation as the triggering factor of the disease but the effects of this accumulation and the cascade of events leading to cognitive decline remain unclear. In mice, we previously showed that amyloid-ÎČ-dependent TRPA1 channel activation triggers hippocampal astrocyte hyperactivity, subsequently inducing hyperactivity in nearby neurons. In this work, we investigated the potential protection against Alzheimer's disease progression provided by early chronic pharmacological inhibition of the TRPA1 channel. A specific inhibitor of TRPA1 channel (HC030031) was administered intraperitoneally from the onset of amyloid-ÎČ overproduction in the APP/PS1-21 mouse model of Alzheimerâs disease. Short-, medium- and long-term effects of this chronic pharmacological TRPA1 blockade were characterized on Alzheimerâs disease progression at functional (astrocytic and neuronal activity), structural, biochemical and behavioural levels. Our results revealed that the first observable disruptions in the Alzheimerâs disease transgenic mouse model used correspond to aberrant hippocampal astrocyte and neuron hyperactivity. We showed that chronic TRPA1 blockade normalizes astrocytic activity, avoids perisynaptic astrocytic process withdrawal, prevents neuronal dysfunction and preserves structural synaptic integrity. These protective effects preserved spatial working memory in this Alzheimerâs disease mouse model. The toxic effect of amyloid-ÎČ on astrocytes triggered by TRPA1 channel activation is pivotal to Alzheimerâs disease progression. TRPA1 blockade prevents irreversible neuronal dysfunction, making this channel a potential therapeutic target to promote neuroprotection
Additional file 2: of TRPA1 channels promote astrocytic Ca2+ hyperactivity and synaptic dysfunction mediated by oligomeric forms of amyloid-ÎČ peptide
Characterization of Fluo-4-loaded cells in the stratum radiatum of mouse coronal slice. (a) Confocal image of Fluo-4-loaded (cyan) and SR101-labeled (magenta) cells in the CA1 stratum radiatum. Merged image showing the proportion of loaded astrocytes (white), confirming that most of the loaded cells are astrocytes. One hour before slicing, animals were iv injected with SR101 as described previously [51]. Vessels are only labeled with SR101 (white arrow). (b) Z-stack projections of confocal images of a patched astrocyte loaded with Fluo-4 (cyan) and SR101 (magenta). Merged image showing the Fluo-4 diffusion in the whole astrocytic territory. (c) Example of a passive whole-cell current recorded in a stratum radiatum astrocyte. Cell was held at â70Â mV and 10Â mV hyper- and depolarizing voltage steps of 80Â ms duration were applied (â110 to +80Â mV). (TIFF 1907 kb
Additional file 7: of TRPA1 channels promote astrocytic Ca2+ hyperactivity and synaptic dysfunction mediated by oligomeric forms of amyloid-ÎČ peptide
TRPA1 channels expression is located in thick GFAP-positive processes and in adjacent thin processes lacking GFAP staining. 3Dârecontsruct of astrocytic processes objectivized by GFAP staining (magenta) showing that TRPA1 channels (green) expression went over in contiguous processes excluding GFAP staining. Scale bar: 50Â nm. (ZIP 1736 kb
Iron Acquisition in Bacillus cereus: The Roles of IlsA and Bacillibactin in Exogenous Ferritin Iron Mobilization
In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A) binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis. Author Summary Iron homeostasis is important for all living organisms; too much iron confers cell toxicity, and too little iron results in reduced cell fitness. While crucial for many cellular processes in both man and pathogens, a battle for this essential nutrient erupts during infection between the host and the invading bacteria. Iron is principally stored in ferritin, a large molecule able to bind several thousand iron ions. Although host ferritins represent a mine of iron for pathogens, studies of the mechanisms involved in its acquisition by bacteria are scarce. In the human opportunistic pathogen Bacillus cereus, the surface protein IlsA is able to bind several host iron sources in vitro. In this study, we show that IlsA acts as a ferritin receptor and enhances iron release from the ferritin through direct interaction with each ferritin subunit. Moreover, we demonstrate that the siderophore bacillibactin, a small secreted iron chelator, is essential for ferritin iron acquisition and takes part in B. cereus virulence. We propose a new iron acquisition model that provides new insights into bacterial host adaptation
Iron acquisition from ferritin relies on bacillibactin production.
<p>Growth kinetics of <i>B. cereus</i> wild type (WT; black square), Î<i>asb</i> petrobactin mutant (blue triangle), Î<i>entA</i> bacillibactin mutant (red circle), complemented <i>ÎentAΩentA</i> strains (purple diamond) and double Î<i>entA</i>Î<i>asb</i> mutant (grey cross). The strains were grown at 37°C in LB medium (<b>A</b>) and in LB medium treated with 2,2âČ-dipyridyl without addition of iron sources (<b>B</b>) or supplemented with 0.3 ”M ferritin only (<b>C</b>) or with 0.3 ”M ferritin and 5 ”M enterobactin (<b>D</b>). Bacterial growth was monitored during 16 hours by measuring the optical density (OD) at 600 nm every hour. Curves are averages of three independent experiments and error bars are SEM from mean values.</p