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effector secreted protein

Kevin Bärlocher, Amanda Welin, Hubert Hilbi
Retrograde trafficking from the endosomal system through the Golgi apparatus back to the endoplasmic reticulum is an essential pathway in eukaryotic cells, serving to maintain organelle identity and to recycle empty cargo receptors delivered by the secretory pathway. Intracellular replication of several bacterial pathogens, including Legionella pneumophila, is restricted by the retrograde trafficking pathway. L. pneumophila employs the Icm/Dot type IV secretion system (T4SS) to form the replication-permissive Legionella-containing vacuole (LCV), which is decorated with multiple components of the retrograde trafficking machinery as well as retrograde cargo receptors...
2017: Frontiers in Cellular and Infection Microbiology
Badreddine Douzi, Laureen Logger, Silvia Spinelli, Stéphanie Blangy, Christian Cambillau, Eric Cascales
The Type VI secretion system (T6SS) is a specialized macromolecular complex dedicated to the delivery of protein effectors into both eukaryotic and bacterial cells. The general mechanism of action of the T6SS is similar to the injection of DNA by contractile bacteriophages. The cytoplasmic portion of the T6SS is evolutionarily, structurally and functionally related to the phage tail complex. It is composed of an inner tube made of stacked Hcp hexameric rings, engulfed within a sheath and built on a baseplate...
December 6, 2017: Journal of Molecular Biology
Alex Z Zaccaron, Burton H Bluhm
Bipolaris cookei (=Bipolaris sorghicola) causes target leaf spot, one of the most prevalent foliar diseases of sorghum. Little is known about the molecular basis of pathogenesis in B. cookei, in large part due to a paucity of resources for molecular genetics, such as a reference genome. Here, a draft genome sequence of B. cookei was obtained and analyzed. A hybrid assembly strategy utilizing Illumina and Pacific Biosciences sequencing technologies produced a draft nuclear genome of 36.1 Mb, organized into 321 scaffolds with L50 of 31 and N50 of 378 kb, from which 11,189 genes were predicted...
December 8, 2017: Scientific Reports
Maximilian Brackmann, Jing Wang, Marek Basler
Secretion systems are essential for bacteria to survive and manipulate their environment. The bacterial type VI secretion system (T6SS) generates the force needed for protein translocation by the contraction of a long polymer called sheath. The sheath is a six-start helical assembly of interconnected VipA/VipB subunits. The mechanism of T6SS sheath contraction is unknown. Here, we show that elongating the N-terminal VipA linker or eliminating charge of a specific VipB residue abolishes sheath contraction and delivery of effectors into target cells...
December 8, 2017: EMBO Reports
Harshavardhan Janga, Liam Cassidy, Fanlu Wang, Dietmar Spengler, Stefanie Oestern-Fitschen, Martin F Krause, Andreas Seekamp, Andreas Tholey, Sabine Fuchs
Infectious agents such as lipopolysaccharides (LPS) challenge the functional properties of the alveolar-capillary barrier (ACB) in the lung. In this study, we analyse the site-specific effects of LPS on the ACB and reveal the effects on the individual cell types and the ACB as a functional unit. Monocultures of H441 epithelial cells and co-cultures of H441 with endothelial cells cultured on Transwells® were treated with LPS from the apical or basolateral compartment. Barrier properties were analysed by the transepithelial electrical resistance (TEER), by transport assays, and immunostaining and assessment of tight junctional molecules at protein level...
December 5, 2017: Journal of Cellular and Molecular Medicine
Haibo Su, Shengling Zhu, Lin Zhu, Cong Kong, Qi Huang, Zhi Zhang, Honghai Wang, Ying Xu
Targeting of Mycobacterium tuberculosis (MTB) latent antigens comprises a crucial strategy for the development of alternative tuberculosis (TB) vaccine(s) that protects against TB reactivation. Here, we generated a multistage DNA vaccine, A39, containing the early antigens Ag85A and Rv3425 as well as the latency-associated protein Rv2029c, which conferred protective immunity in a pre-exposure mouse model. Moreover, administration of the A39 vaccination after MTB exposure inhibited reactivation and resulted in significantly lower bacterial loads in the lungs and spleen of mice, compared to those in the control population...
2017: Frontiers in Microbiology
Jianpo Xu, Dandan Xu, Muyang Wan, Li Yin, Xiaofei Wang, Lijie Wu, Yanhua Liu, Xiaoyun Liu, Yan Zhou, Yongqun Zhu
The type IVb secretion system (T4BSS) of Legionella pneumophila is a multiple-component apparatus that delivers ∼300 virulent effector proteins into host cells. The injected effectors modulate host cellular processes to promote bacterial infection and proliferation. IcmS and IcmW are two conserved small, acidic adaptor proteins that form a binary complex to interact with many effectors and facilitate their translocation. IcmS and IcmW can also interact with DotL, an ATPase of the type IV coupling protein complex (T4CP)...
December 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
Mohammed Bensellam, Jean-Christophe Jonas, D Ross Laybutt
Like all the cells of an organism, pancreatic β-cells originate from embryonic stem cells through a complex cellular process termed differentiation. Differentiation involves the coordinated and tightly controlled activation/repression of specific effectors and gene clusters in a time-dependent fashion thereby giving rise to particular morphological and functional cellular features. Interestingly, cellular differentiation is not a unidirectional process. Indeed, growing evidence suggests that under certain conditions, mature β-cells can lose, to various degrees, their differentiated phenotype and cellular identity and regress to a less differentiated or a precursor-like state...
December 4, 2017: Journal of Endocrinology
Jamie McGowan, David A Fitzpatrick
The oomycetes are a class of microscopic, filamentous eukaryotes within the stramenopiles-alveolate-Rhizaria (SAR) supergroup and include ecologically significant animal and plant pathogens. Oomycetes secrete large arsenals of effector proteins that degrade host cell components, manipulate host immune responses, and induce necrosis, enabling parasitic colonization. This study investigated the expansion and evolution of effectors in 37 oomycete species in 4 oomycete orders, including Albuginales, Peronosporales, Pythiales, and Saprolegniales species...
November 2017: MSphere
Bo Pang, Sungjoon Kim, Daiqing Li, Zejun Ma, Bei Sun, Xiaona Zhang, Zhongming Wu, Liming Chen
The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+ permeable channel activated by cAMP, is expressed on pancreatic β-cells and is responsible for the regulation of insulin secretion. It is known that glucose-stimulated insulin secretion (GSIS) can be potentiated by glucagon like peptide-1 (GLP-1), and that the changes in the extracellular glucose concentration alter the levels of intracellular adenosine ATP and cAMP. The present study hypothesized that TRPM2 mediates the modulatory effect of GLP-1 on insulin secretion...
November 2017: Experimental and Therapeutic Medicine
Srayan Ghosh, Poonam Kanwar, Gopaljee Jha
Sheath blight disease is one of the predominant diseases of rice and it is caused by the necrotrophic fungal pathogen Rhizoctonia solani. The mechanistic insight about its widespread success as a broad host range pathogen is limited. In this study, we endeavor to identify pathogenicity determinants of R. solani during infection process in rice. Through RNAseq analysis, we identified a total of 65 and 232 R. solani (strain BRS1) genes to be commonly upregulated in three different rice genotypes (PB1, Tetep, and TP309) at establishment and necrotrophic phase, respectively...
December 1, 2017: Current Genetics
Su San Toh, Zehua Chen, Eric C Rouchka, David J Schultz, Christina A Cuomo, Michael H Perlin
The successful interaction between pathogen/parasite and host requires a delicate balance between fitness of the former and survival of the latter. To optimize fitness a parasite/pathogen must effectively create an environment conducive to reproductive success, while simultaneously avoiding or minimizing detrimental host defense response. The association between Microbotryum lychnidis-dioicae and its host, Silene latifolia, serves as an excellent model to examine such interactions. This fungus is part of a species complex that infects species of the Caryophyllaceae, replacing pollen with the fungal spores...
December 1, 2017: G3: Genes—Genomes—Genetics
Nargisse El Hajjami, Simon Moussa, Jonathan Houssa, Daniel Monteyne, David Perez-Morga, Anne Botteaux
The virulence of Shigella mainly resides in the use of a Type 3 Secretion System (T3SS) to inject several proteins inside the host cell. Three categories of proteins are hierarchically secreted: (1) the needle components (MxiH and MxiI), (2) the translocator proteins which form a pore (translocon) inside the host cell membrane, and (3) the effectors interfering with the host cell signaling pathways. In the absence of host cell contact, the T3SS is maintained in an "off" state by the presence of a tip complex...
December 1, 2017: MicrobiologyOpen
Gaëtan Vanier, Szymon Stelter, Jessica Vanier, Franziska Hempel, Uwe G Maier, Patrice Lerouge, Julian Ma, Muriel Bardor
Microalgae are unicellular eukaryotic organisms which represent an emerging alternative to other cell biofactories commonly used to produce monoclonal antibodies. Microalgae display several biotechnological advantages such as their rapid growth rate and their phototrophic lifestyle allowing low production costs as protein expression is solar-fueled. Recently, a fully-assembled recombinant IgG antibody directed against Hepatitis B surface antigen was produced and secreted in the culture medium of the diatom Phaeodactylum tricornutum...
November 30, 2017: Biotechnology Journal
Madhvi Soni, Kalyan K Mondal
Xanthomonas axonopodis pv. punicae (Xap) causing bacterial blight is an important pathogen that incurs significant losses to the exportability of pomegranate. Xap employs Xop TTSS-effector via type three secretion system to suppress pomegranate immunity. Here, we investigate the role of XopL during blight pathogenesis. We found that XopL is essential for its in planta growth and full virulence. Leaves inoculated with Xap ΔxopL produced restricted water-soaked lesions compared to that inoculated with Xap wild...
November 29, 2017: Journal of Integrative Plant Biology
Soma Ghosh, Tamara J O'Connor
Redundancy has been referred to as a state of no longer being needed or useful. Microbiologists often theorize that the only case of true redundancy in a haploid organism would be a recent gene duplication event, prior to divergence through selective pressure. However, a growing number of examples exist where an organism encodes two genes that appear to perform the same function. For example, many pathogens translocate multiple effector proteins into hosts. While disruption of individual effector genes does not result in a discernable phenotype, deleting genes in combination impairs pathogenesis: this has been described as redundancy...
2017: Frontiers in Cellular and Infection Microbiology
Jiawei Wang, Bingjiao Yang, Yi An, Tatiana Marquez-Lago, André Leier, Jonathan Wilksch, Qingyang Hong, Yang Zhang, Morihiro Hayashida, Tatsuya Akutsu, Geoffrey I Webb, Richard A Strugnell, Jiangning Song, Trevor Lithgow
In the course of infecting their hosts, pathogenic bacteria secrete numerous effectors, namely, bacterial proteins that pervert host cell biology. Many Gram-negative bacteria, including context-dependent human pathogens, use a type IV secretion system (T4SS) to translocate effectors directly into the cytosol of host cells. Various type IV secreted effectors (T4SEs) have been experimentally validated to play crucial roles in virulence by manipulating host cell gene expression and other processes. Consequently, the identification of novel effector proteins is an important step in increasing our understanding of host-pathogen interactions and bacterial pathogenesis...
November 27, 2017: Briefings in Bioinformatics
Thomas Timm, Giada Annoscia, Jochen Klein, Günter Lochnit
Proteins and glycolipids have been found to be decorated with phosphorylcholine (PC) both in protozoa and nematodes that parasitize humans and animals. PC epitopes can provoke various effects on immune cells leading to an immunomodulation of the host's immune system that allows long-term persistence of the parasites. So far, only a limited number of PC-modified proteins, mainly from nematodes, have been identified. Infections caused by Leishmania spp. (e.g., L. infantum in southern Europe) affect about 12 million people worldwide and are characterized by a wide spectrum of clinical forms in humans, ranging from cutaneous to fatal visceral leishmaniasis...
November 29, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Maria Chatzidaki-Livanis, Michael J Coyne, Kevin G Roelofs, Rahul R Gentyala, Jarreth M Caldwell, Laurie E Comstock
Human gut Bacteroides species produce different types of toxins that antagonize closely related members of the gut microbiota. Some are toxic effectors delivered by type VI secretion systems, and others are non-contact-dependent secreted antimicrobial proteins. Many strains of Bacteroides fragilis secrete antimicrobial molecules, but only one of these toxins has been described to date (Bacteroidales secreted antimicrobial protein 1 [BSAP-1]). In this study, we describe a novel secreted protein produced by B...
November 28, 2017: MBio
Shintaro Matsuba, Toshiki Yabe-Wada, Kazuya Takeda, Tetsuya Sato, Mikita Suyama, Toshiyuki Takai, Toshiaki Kikuchi, Toshihiro Nukiwa, Akira Nakamura
Mast cells, basophils, and eosinophils are central effectors in allergic inflammatory disorders. These cells secrete abundant serine proteases as well as chemical mediators and cytokines; however, the expression profiles and functions of their endogenous inhibitors remain elusive. We found that murine secretory leukoprotease inhibitor (SLPI) is expressed in basophils and eosinophils but in not in mast cells. SLPI-deficient (Slpi-/-) basophils produce more cytokines than wild-type mice after IgE stimulation...
2017: Frontiers in Immunology
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