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Apoptosis anaplasma

Alejandro Cabezas-Cruz, Pilar Alberdi, Nieves Ayllón, James J Valdés, Raymond Pierce, Margarita Villar, José de la Fuente
Epigenetic mechanisms have not been characterized in ticks despite their importance as vectors of human and animal diseases worldwide. The objective of this study was to characterize the histones and histone modifying enzymes (HMEs) of the tick vector Ixodes scapularis and their role during Anaplasma phagocytophilum infection. We first identified 5 histones and 34 HMEs in I. scapularis in comparison with similar proteins in model organisms. Then, we used transcriptomic and proteomic data to analyze the mRNA and protein levels of I...
April 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Pilar Alberdi, Karen L Mansfield, Raúl Manzano-Román, Charlotte Cook, Nieves Ayllón, Margarita Villar, Nicholas Johnson, Anthony R Fooks, José de la Fuente
Anaplasma phagocytophilum are transmitted by Ixodes spp. ticks and have become one of the most common and relevant tick-borne pathogens due to their impact on human and animal health. Recent results have increased our understanding of the molecular interactions between Ixodes scapularis and A. phagocytophilum through the demonstration of tissue-specific molecular pathways that ensure pathogen infection, development and transmission by ticks. However, little is known about the Ixodes ricinus genes and proteins involved in the response to A...
2016: Frontiers in Cellular and Infection Microbiology
Margarita Villar, Nieves Ayllón, Pilar Alberdi, Andrés Moreno, María Moreno, Raquel Tobes, Lourdes Mateos-Hernández, Sabine Weisheit, Lesley Bell-Sakyi, José de la Fuente
Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human granulocytic anaplasmosis. These intracellular bacteria establish infection by affecting cell function in both the vertebrate host and the tick vector, Ixodes scapularis. Previous studies have characterized the tick transcriptome and proteome in response to A. phagocytophilum infection. However, in the postgenomic era, the integration of omics datasets through a systems biology approach allows network-based analyses to describe the complexity and functionality of biological systems such as host-pathogen interactions and the discovery of new targets for prevention and control of infectious diseases...
December 2015: Molecular & Cellular Proteomics: MCP
Pilar Alberdi, Nieves Ayllón, Alejandro Cabezas-Cruz, Lesley Bell-Sakyi, Erich Zweygarth, Snorre Stuen, José de la Fuente
Anaplasma phagocytophilum is an intracellular rickettsial pathogen transmitted by Ixodes spp. ticks, which causes granulocytic anaplasmosis in humans, horses and dogs and tick-borne fever (TBF) in ruminants. In the United States, human granulocytic anaplasmosis (HGA) is highly prevalent while TBF has not been reported. However, in Europe the situation is the opposite, with high prevalence for TBF in sheep and low prevalence of HGA. The origin of these differences has not been identified and our hypothesis is that different A...
September 2015: Ticks and Tick-borne Diseases
David H Walker, J Stephen Dumler
Arthropod-borne obligately intracellular bacteria pose a difficult challenge to the immune system. The genera Rickettsia, Orientia, Ehrlichia, and Anaplasma evolved mechanisms of immune evasion, and each interacts differently with the immune system. The roles of CD8 T cells include protective immunity and immunopathology. In Rickettsia infections, CD8 T cells are protective mediated in part by cytotoxicity toward infected cells. In contrast, TNF-α overproduction by CD8 T cells is pathogenic in lethal ehrlichiosis by induction of apoptosis/necrosis in hepatocytes...
May 2015: Seminars in Immunopathology
Nieves Ayllón, Margarita Villar, Ruth C Galindo, Katherine M Kocan, Radek Šíma, Juan A López, Jesús Vázquez, Pilar Alberdi, Alejandro Cabezas-Cruz, Petr Kopáček, José de la Fuente
Anaplasma phagocytophilum is an emerging pathogen that causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects cell function in both vertebrate host and the tick vector, Ixodes scapularis. Global tissue-specific response and apoptosis signaling pathways were characterized in I. scapularis nymphs and adult female midguts and salivary glands infected with A. phagocytophilum using a systems biology approach combining transcriptomics and proteomics. Apoptosis was selected for pathway-focused analysis due to its role in bacterial infection of tick cells...
March 2015: PLoS Genetics
Hua Niu, Yasuko Rikihisa
The modulation of host cell apoptosis by bacterial pathogens is critical for their intracellular survival. Several intracellular bacteria achieve this by secreting proteins that interact with apoptosis pathways to inhibit host cell apoptosis. Anaplasma phagocytophilum, which causes human granulocytic anaplasmosis, is such bacterium. The protein Ats-1, translocated from A. phagocytophilum by the bacterial type IV secretion system, localizes to host cell mitochondria, and interferes with apoptosis induction. In this chapter, we present a protocol applied to investigate an anti-apoptotic effect of Ats-1...
2014: Methods in Molecular Biology
Z Woldehiwet, C Yavari
Anaplasma phagocytophilum, the causative agent of tick-borne fever (TBF) in sheep and cattle and human granulocytic anaplasmosis, has the unique ability to selectively infect and multiply within the hostile environment of the neutrophil. Previous studies have shown that sheep with TBF are more susceptible to other infections and that infected neutrophils have reduced phagocytic ability and delayed apoptosis. This suggests that survival of A. phagocytophilum in these short-lived cells involves the ability to subvert or resist their bacterial killing, but also to modify the host cells such that the host cells survive long after infection...
May 2014: Journal of Comparative Pathology
Maiara S Severo, Anthony Choy, Kimberly D Stephens, Olivia S Sakhon, Gang Chen, Duk-Won D Chung, Karine G Le Roch, Gregor Blaha, Joao H F Pedra
Ubiquitination is a posttranslational modification that regulates protein degradation and signaling in eukaryotes. Although it is acknowledged that pathogens exploit ubiquitination to infect mammalian cells, it remains unknown how microbes interact with the ubiquitination machinery in medically relevant arthropods. Here, we show that the ubiquitination machinery is present in the tick Ixodes scapularis and demonstrate that the E3 ubiquitin ligase named x-linked inhibitor of apoptosis protein (XIAP) restricts bacterial colonization of this arthropod vector...
December 1, 2013: Journal of Infectious Diseases
Nieves Ayllón, Margarita Villar, Ann T Busby, Katherine M Kocan, Edmour F Blouin, Elena Bonzón-Kulichenko, Ruth C Galindo, Atilio J Mangold, Pilar Alberdi, José M Pérez de la Lastra, Jesús Vázquez, José de la Fuente
Anaplasma phagocytophilum causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects gene expression in both the vertebrate host and the tick vector, Ixodes scapularis. Here, we identified new genes, including spectrin alpha chain or alpha-fodrin (CG8) and voltage-dependent anion-selective channel or mitochondrial porin (T2), that are involved in A. phagocytophilum infection/multiplication and the tick cell response to infection. The pathogen downregulated the expression of CG8 in tick salivary glands and T2 in both the gut and salivary glands to inhibit apoptosis as a mechanism to subvert host cell defenses and increase infection...
July 2013: Infection and Immunity
R Dhamodharan, Sl Hoti, G Sivapragasam, Mk Das
BACKGROUND: Periplasmic serine proteases of HtrA type of Wolbachia have been shown to play a role in the pathogenesis of filarial disease. AIMS: This study was aimed to sequence Wb-HtrA serine protease and analyze its phylogenetic position by comparing with other filarial and non-filarial nematode homologs. MATERIALS AND METHODS: Partial HtrA gene fragment was amplified from DNA isolated from periodic and sub-periodic Wuchereria bancrofti parasites collected from Pondicherry and Nicobar islands, respectively...
July 2011: Tropical Parasitology
Hua Niu, Qingming Xiong, Akitsugu Yamamoto, Mitsuko Hayashi-Nishino, Yasuko Rikihisa
Autophagy, a cytoplasmic catabolic process, plays a critical role in defense against intracellular infection. In turn, evasion or inhibition of autophagy has emerged as an important virulence factor for intracellular pathogens. However, Anaplasma phagocytophilum, the obligatory intracellular bacterium that causes human granulocytic anaplasmosis, replicates in the membrane-bound compartment resembling early autophagosome. Here, we found that Anaplasma translocated substrate 1 (Ats-1), a type IV secretion effector, binds Beclin 1, a subunit of the class III PI3K and Atg14L, and it nucleates autophagosomes with markers of omegasomes, double FYVE-containing protein 1, Atg14L, and LC3...
December 18, 2012: Proceedings of the National Academy of Sciences of the United States of America
Arup Sarkar, Lars Hellberg, Asima Bhattacharyya, Martina Behnen, Keqing Wang, Janet M Lord, Sonja Möller, Maja Kohler, Werner Solbach, Tamás Laskay
Anaplasma phagocytophilum, a Gram-negative, obligate intracellular bacterium infects primarily neutrophil granulocytes. Infection with A. phagocytophilum leads to inhibition of neutrophil apoptosis and consequently contributes to the longevity of the host cells. Previous studies demonstrated that the infection inhibits the executionary apoptotic machinery in neutrophils. However, little attempt has been made to explore which survival signals are modulated by the pathogen. The aim of the present study was to clarify whether the phosphatidylinositol 3-kinase (PI3K)/Akt and NF-κB signaling pathways, which are considered as important survival pathways in neutrophils, are involved in A...
April 2012: Infection and Immunity
Pratap Karki, Jacob W Ijdo
Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, is an obligate intra-cellular bacterium that survives in neutrophils by delaying apoptosis. The human promyelocytic leukemia cell line HL-60 has been the ultimate choice for culturing Anaplasma in vitro. In this study, we assessed the various events of drug-induced apoptosis in A. phagocytophilum-infected HL-60 cells. Anaplasma infection reduced the cell viability and increased the apoptosis in HL-60 cells and staurosporine or etoposide-induced apoptosis was further exacerbated with Anaplasma infection...
November 1, 2011: World Journal of Microbiology & Biotechnology
Sushan Han, Junzo Norimine, Kelly A Brayton, Guy H Palmer, Glen A Scoles, Wendy C Brown
Control of blood-borne infections is dependent on antigen-specific effector and memory T cells and high-affinity IgG responses. In chronic infections characterized by a high antigen load, it has been shown that antigen-specific T and B cells are vulnerable to downregulation and apoptosis. Anaplasma marginale is a persistent infection of cattle characterized by acute and chronic high-load bacteremia. We previously showed that CD4(+) T cells primed by immunization with an A. marginale outer membrane protein were rapidly deleted following infection...
December 2010: Clinical and Vaccine Immunology: CVI
Yasuko Rikihisa
Anaplasma spp. and Ehrlichia spp. cause several emerging human infectious diseases. Anaplasma phagocytophilum and Ehrlichia chaffeensis are transmitted between mammals by blood-sucking ticks and replicate inside mammalian white blood cells and tick salivary-gland and midgut cells. Adaptation to a life in eukaryotic cells and transmission between hosts has been assisted by the deletion of many genes that are present in the genomes of free-living bacteria (including genes required for the biosynthesis of lipopolysaccharide and peptidoglycan), by the acquisition of a cholesterol uptake pathway and by the expansion of the repertoire of genes encoding the outer-membrane porins and type IV secretion system...
May 2010: Nature Reviews. Microbiology
Hua Niu, Vera Kozjak-Pavlovic, Thomas Rudel, Yasuko Rikihisa
Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, infects human neutrophils and inhibits mitochondria-mediated apoptosis. Bacterial factors involved in this process are unknown. In the present study, we screened a genomic DNA library of A. phagocytophilum for effectors of the type IV secretion system by a bacterial two-hybrid system, using A. phagocytophilum VirD4 as bait. A hypothetical protein was identified as a putative effector, hereby named Anaplasmatranslocated substrate 1 (Ats-1)...
February 2010: PLoS Pathogens
Yasuko Rikihisa
Ehrlichia chaffeensis and Anaplasma phagocytophilum are obligatory intracellular bacteria that preferentially replicate inside leukocytes by utilizing biological compounds and processes of these primary host defensive cells. These bacteria incorporate cholesterol from the host for their survival. Upon interaction with host monocytes and granulocytes, respectively, these bacteria usurp the lipid raft domain containing GPI-anchored protein to induce a series of signaling events that result in internalization of the bacteria...
February 10, 2010: Veterinary Parasitology
D D Carrade, J E Foley, D L Borjesson, J E Sykes
Anaplasma phagocytophilum is an emerging pathogen of humans, horses, and dogs worldwide that is transmitted by Ixodid ticks and maintained in a variety of small wild mammal species. Recent studies suggest that multiple strains of A. phagocytophilum may be circulating in wild and domestic animal populations, and these strains may have differential host tropisms and pathogenicity. The organism infects and survives within neutrophils by disabling key neutrophil functions, including neutrophil motility, phagocytosis, the oxidative burst mechanism, and neutrophil-endothelial cell interactions, as well as interfering with neutrophil apoptosis...
November 2009: Journal of Veterinary Internal Medicine
Hin C Lee, Mitomu Kioi, Jing Han, Raj K Puri, Jesse L Goodman
Anaplasma phagocytophilum (Ap), the etiologic agent of the tick-borne disease human granulocytic anaplasmosis, is an obligate intracellular pathogen unique in its ability to target and replicate within neutrophils. We define and compare the spectra of host gene expression in response to Ap infection of human neutrophils and of HL-60 cells using long (70-mer)-oligonucleotide array technology. In addition to apoptosis-related genes, genes involved in signaling pathways, transcriptional regulation, immune response, host defense, cell adhesion, and cytoskeleton were modulated in neutrophils infected with Ap...
September 2008: Genomics
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