共查询到20条相似文献,搜索用时 0 毫秒
1.
Roderick F Felsheim Michael J Herron Curtis M Nelson Nicole Y Burkhardt Anthony F Barbet Timothy J Kurtti Ulrike G Munderloh 《BMC biotechnology》2006,6(1):42-9
Background
Tick-borne pathogens cause emerging zoonoses, and include fastidious organisms such as Anaplasma phagocytophilum. Because of their obligate intracellular nature, methods for mutagenesis and transformation have not been available. 相似文献2.
3.
Anaplasma phagocytophilum, the etiologic agent of human granulocytic anaplasmosis (HGA), has genes predicted to encode three sensor kinases, one of which is annotated PleC, and three response regulators, one of which is PleD. Prior to this study, the roles of PleC and PleD in the obligatory intracellular parasitism of A. phagocytophilum and their biochemical activities were unknown. The present study illustrates the relevance of these factors by demonstrating that both pleC and pleD were expressed in an HGA patient. During A. phagocytophilum development in human promyelocytic HL-60 cells, PleC and PleD were synchronously upregulated at the exponential growth stage and downregulated prior to extracellular release. A recombinant PleC kinase domain (rPleCHKD) has histidine kinase activity; no activity was observed when the conserved site of phosphorylation was replaced with alanine. A recombinant PleD (rPleD) has autokinase activity using phosphorylated rPleCHKD as the phosphoryl donor but not with two other recombinant histidine kinases. rPleCHKD could not serve as the phosphoryl donor for a mutant rPleD (with a conserved aspartic acid, the site of phosphorylation, replaced by alanine) or two other A. phagocytophilum recombinant response regulators. rPleD had diguanylate cyclase activity to generate cyclic (c) di-GMP from GTP in vitro. UV cross-linking of A. phagocytophilum lysate with c-di-[(32)P]GMP detected an approximately 47-kDa endogenous protein, presumably c-di-GMP downstream receptor. A new hydrophobic c-di-GMP derivative, 2'-O-di(tert-butyldimethylsilyl)-c-di-GMP, inhibited A. phagocytophilum infection in HL-60 cells. Our results suggest that the two-component PleC-PleD system is a diguanylate cyclase and that a c-di-GMP-receptor complex regulates A. phagocytophilum intracellular infection. 相似文献
4.
5.
嗜吞噬细胞无形体致病机理的研究进展 总被引:1,自引:0,他引:1
嗜吞噬细胞无形体是一种侵染中性粒细胞专性细胞内寄生的革兰阴性菌,其所致疾病为人粒细胞无形体病(HGA),是一种经蜱传播的人兽共患病。它感染中性粒细胞后可诱发机体产生炎症免疫反应,最终导致免疫抑制及潜在疾病引起的各种继发感染和器官衰竭,甚至危及生命。近年来该病原体日益受到人们的关注和重视。就嗜吞噬细胞无形体致病机理研究的进展进行了综述。 相似文献
6.
7.
Since posttranslational modification (PTM) by the small ubiquitin-related modifiers (SUMOs) was discovered over a decade ago, a huge number of cellular proteins have been found to be reversibly modified, resulting in alteration of differential cellular pathways. Although the molecular consequences of SUMO attachment are difficult to predict, the underlying principle of SUMOylation is altering inter- and/or intramolecular interactions of the modified substrate, changing localization, stability, and/or activity. Unsurprisingly, many different pathogens have evolved to exploit the cellular SUMO modification system due to its functional flexibility and far-reaching functional downstream consequences. Although the extensive knowledge gained so far is impressive, a definitive conclusion about the role of SUMO modification during virus infection in general remains elusive and is still restricted to a few, yet promising concepts. Based on the available data, this review aims, first, to provide a detailed overview of the current state of knowledge and, second, to evaluate the currently known common principles/molecular mechanisms of how human pathogenic microbes, especially viruses and their regulatory proteins, exploit the host cell SUMO modification system. 相似文献
8.
9.
Invasion and survival strategies of Anaplasma phagocytophilum 总被引:4,自引:4,他引:0
Anaplasma phagocytophilum is an aetiological agent of human granulocytic ehrlichiosis, an emerging tick‐borne zoonosis in the United States and Europe. This obligate intracellular bacterium is unique in that it colonizes polymorphonuclear leucocytes (neutrophils). Neutrophils are key players in innate immunity. These short‐lived phagocytes ingest invading microorganisms and destroy them by various means, which include fusing the bacteria‐containing phagosome with acidic lysosomes as well as directing toxic oxidative and proteolytic compounds into the phagosomal lumen. Its tropism for neutrophils indicates that A. phagocytophilum uses strategies for evading and/or neutralizing these microbicidal activities. This review focuses on some of the mechanisms that A. phagocytophilum uses for neutrophil adhesion, surviving within the hostile intracellular environment of its host neutrophil and for effectively disseminating to naïve host cells. 相似文献
10.
Anaplasma phagocytophilum is a bacterium that is transmitted by Ixodes spp. ticks, in which it resides in salivary glands. Ticks inoculate the pathogen into hosts together with an array of salivary molecules that reduce host anti-tick inflammation. Sukumaran et al. recently showed that A. phagocytophilum uses a tick salivary protein, Salp16, to enhance its uptake from the host and into the salivary gland. Occupation and exploitation of tick salivary glands have implications for the maintenance and detection of A. phagocytophilum in its vector and early pathogen interactions with its hosts. 相似文献
11.
Subversion of cellular autophagy by Anaplasma phagocytophilum 总被引:1,自引:0,他引:1
Anaplasma phagocytophilum , the causative agent of human granulocytic anaplasmosis, is an obligatory intracellular pathogen. After entry into host cells, the bacterium is diverted from the endosomal pathway and replicates in a membrane-bound compartment devoid of endosomal or lysosomal markers. Here, we show that several hallmarks of early autophagosomes can be identified in A. phagocytophilum replicative inclusions, including a double-lipid bilayer membrane and colocalization with GFP-tagged LC3 and Beclin 1, the human homologues of Saccharomyces cerevisiae autophagy-related proteins Atg8 and Atg6 respectively. While the membrane-associated form of LC3, LC3-II, increased during A. phagocytophilum infection, A. phagocytophilum -containing inclusions enveloped with punctate GFP-LC3 did not colocalize with a lysosomal marker. Stimulation of autophagy by rapamycin favoured A. phagocytophilum infection. Inhibition of the autophagosomal pathway by 3-methyladenine did not inhibit A. phagocytophilum internalization, but reversibly arrested its growth. Although autophagy is considered part of the innate immune system that clears a variety of intracellular pathogens, our study implies that A. phagocytophilum subverts this system to establish itself in an early autophagosome-like compartment segregated from lysosomes to facilitate its proliferation. 相似文献
12.
Dumler JS 《FEMS immunology and medical microbiology》2012,64(1):13-20
Anaplasma phagocytophilum causes granulocytic anaplasmosis, an acute disease in humans that is also often subclinical. However, 36% are hospitalized, 7% need intensive care, and the case fatality rate is 0.6%. The biological basis for severe disease is not understood. Despite A.?phagocytophilum's mechanisms to subvert neutrophil antimicrobial responses, whether these mechanisms lead to disease is unclear. In animals, inflammatory lesions track with IFNγ and IL-10 expression and infection of Ifng(-/-) mice leads to increased pathogen load but inhibition of inflammation. Suppression of STAT signaling in horses impacts IL-10 and IFN-γ expression, and also suppresses disease severity. Similar inhibition of inflammation with infection of NKT-deficient mice suggests that innate immune responses are key for disease. With severe disease, tissues can demonstrate hemophagocytosis, and measures of macrophage activation/hemophagocytic syndromes (MAS/HPS) support the concept of human granulocytic anaplasmosis as an immunopathologic disease. MAS/HPS are related to defective cytotoxic lymphocytes that ordinarily diminish inflammation. Pilot studies in mice show cytotoxic lymphocyte activation with A.?phagocytophilum infection, yet suppression of cytotoxic responses from both NKT and CD8 cells, consistent with the development of MAS/HPS. Whether severity relates to microbial factors or genetically determined diversity in human immune and inflammatory response needs more investigation. 相似文献
13.
Detection of tick‐borne Anaplasma bovis,Anaplasma phagocytophilum and Anaplasma centrale in Spain
下载免费PDF全文
![点击此处可从《Medical and veterinary entomology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A. M. PALOMAR A. PORTILLO P. SANTIBÁÑEZ D. MAZUELAS L. RONCERO L. GARCÍA‐ÁLVAREZ S. SANTIBÁÑEZ Ó. GUTIÉRREZ J. A. OTEO 《Medical and veterinary entomology》2015,29(3):349-353
The genus Anaplasma (Rickettsiales: Anaplasmataceae) includes species of medical and veterinary importance. The presence of Anaplasma spp. in ticks from birds, as well as in Haemaphysalis punctata (Ixodida: Ixodidae) specimens collected from cattle and vegetation in northern Spain was investigated. A total of 336 ticks from birds [174 Ixodes frontalis (Ixodida: Ixodidae), 108 H. punctata, 34 Hyalomma marginatum (Ixodida: Ixodidae), 17 Ixodes ricinus (Ixodida: Ixodidae) and three Ixodes spp.], and 181 H. punctata specimens collected from cattle (n = 71) and vegetation (n = 110) were analysed. Anaplasma bovis was detected in five H. punctata, including two from birds (1.9%) and three from vegetation (2.7%). Four I. frontalis (2.3%) (one co‐infected with ‘Candidatus Midichloria mitochondrii’) and one I. ricinus (5.9%) removed from birds, as well as four H. punctata (5.6%) collected from cattle showed Anaplasma phagocytophilum infection. In addition, Anaplasma centrale was found in two H. punctata, one from a cow (1.4%) and the other from vegetation (0.9%). This study represents the first evidence of the presence of A. bovis in European ticks, and reports the first detection of A. bovis and A. centrale in H. punctata, and the first finding of A. phagocytophilum and ‘Ca. Midichloria mitochondrii’ in I. frontalis. 相似文献
14.
Joao H. F. Pedra Sukanya Narasimhan Dubravko Rendić Kathleen DePonte Lesley Bell‐Sakyi Iain B. H. Wilson Erol Fikrig 《Cellular microbiology》2010,12(9):1222-1234
Fucosylated structures participate in a wide range of pathological processes in eukaryotes and prokaryotes. The impact of fucose on microbial pathogenesis, however, has been less appreciated in arthropods of medical relevance. Thus, we used the tick‐borne bacterium Anaplasma phagocytophilum– the agent of human granulocytic anaplasmosis to understand these processes. Here we show that A. phagocytophilum uses α1,3‐fucose to colonize ticks. We demonstrate that A. phagocytophilum modulates the expression of α1,3‐fucosyltransferases and gene silencing significantly reduces colonization of tick cells. Acquisition but not transmission of A. phagocytophilum was affected when α1,3‐fucosyltransferases were silenced during tick feeding. Our results uncover a novel mechanism of pathogen colonization in arthropods. Decoding mechanisms of pathogen invasion in ticks might expedite the development of new strategies to interfere with the life cycle of A. phagocytophilum. 相似文献
15.
16.
17.
Bindu Sukumaran Sarah Fankhauser Pradeep D. Uchil Roie Levy Morven Graham Tonya Michelle Colpitts Erol Fikrig 《Cellular microbiology》2011,13(1):47-61
Anaplasma phagocytophilum causes human granulocytic anaplasmosis, one of the most common tick‐borne diseases in North America. This unusual obligate intracellular pathogen selectively persists within polymorphonuclear leucocytes. In this study, using the yeast surrogate model we identified an A. phagocytophilum virulence protein, AptA (A. phagocytophilum toxin A), that activates mammalian Erk1/2 mitogen‐activated protein kinase. This activation is important for A. phagocytophilum survival within human neutrophils. AptA interacts with the intermediate filament protein vimentin, which is essential for A. phagocytophilum‐induced Erk1/2 activation and infection. A. phagocytophilum infection reorganizes vimentin around the bacterial inclusion, thereby contributing to intracellular survival. These observations reveal a major role for the bacterial protein, AptA, and the host protein, vimentin, in the activation of Erk1/2 during A. phagocytophilum infection. 相似文献
18.
Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, is an obligate intracellular 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. Altogether our results suggest that A.
phagocytophilum infection is proapoptotic in HL-60 cells unlike in neutrophils where it is antiapoptotic. 相似文献
19.
Erik G Granquist Kjetil Bårdsen Karin Bergström Snorre Stuen 《Acta veterinaria Scandinavica》2010,52(1):1-7