Abstract:
:Intracellular bacterial pathogens evade the bactericidal functions of mammalian cells by physical escape from their phagosome and replication into the cytoplasm or through the modulation of phagosome maturation and biogenesis of a membrane-bound replicative organelle. Here, we detail in murine primary macrophages the intracellular life cycle of Francisella tularensis, a highly infectious bacterium that survives and replicates within mammalian cells. After transient interactions with the endocytic pathway, bacteria escaped from their phagosome by 1 h after infection and underwent replication in the cytoplasm from 4 to 20 h after infection. Unexpectedly, the majority of bacteria were subsequently found to be enclosed within large, juxtanuclear, LAMP-1-positive vacuoles called Francisella-containing vacuoles (FCVs). FCV formation required intracytoplasmic replication of bacteria. Using electron and fluorescence microscopy, we observed that the FCVs contained morphologically intact bacteria, despite fusing with lysosomes. FCVs are multimembranous structures that accumulate monodansylcadaverine and display the autophagy-specific protein LC3 on their membrane. Formation of FCVs was significantly inhibited by 3-methyladenine, confirming a role for the autophagic pathway in the biogenesis of these organelles. Taken together, our results demonstrate that, via autophagy, F. tularensis reenters the endocytic pathway after cytoplasmic replication, a process thus far undescribed for intracellular pathogens.
journal_name
Proc Natl Acad Sci U S Aauthors
Checroun C,Wehrly TD,Fischer ER,Hayes SF,Celli Jdoi
10.1073/pnas.0601838103subject
Has Abstractpub_date
2006-09-26 00:00:00pages
14578-83issue
39eissn
0027-8424issn
1091-6490pii
0601838103journal_volume
103pub_type
杂志文章abstract::We have selected from a mixture of random polynucleotides an RNA that is able to replicate in the presence of the DNA-dependent RNA polymerase of Escherichia coli, provided the medium contains Mn(2+) and ITP, in addition to ATP, CTP, and UTP. The RNA consists of a chain of about 125 (+/-25) nucleotides and appears to ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.3.934
更新日期:1973-03-01 00:00:00
abstract::A monomorphic anti-HLA-G monoclonal antibody (mAb) was obtained by immunization of HLA-B27/human beta 2-microglobulin double-transgenic mice with transfected murine L cells expressing both HLA-G and human beta 2-microglobulin. This mAb, designated BFL.1, specifically recognizes, by flow cytometry analysis, the immuniz...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.22.10292
更新日期:1995-10-24 00:00:00
abstract::The time course of thermal reactions after illumination of 100% humidified bacteriorhodopsin films was followed with FTIR spectroscopy between 125 and 195 K. We monitored the conversion of the initial photoproduct, K, to the next, L intermediate, and a shunt reaction of the L state directly back to the initial BR stat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0703859104
更新日期:2007-06-05 00:00:00
abstract::The DNA in chromatin of isolated thymus nuclei, and in two different preparations of deoxyribonucleoprotein extracted from chromatin, has been digested with DNase. By variation of the time of reaction and the concentration of enzyme, and by comparison of the action of the enzyme on (protein-free) DNA with its action o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.12.2945
更新日期:1971-12-01 00:00:00
abstract::CCAAT/enhancer binding protein (C/EBP) epsilon is a recently cloned member of the C/EBP family of transcription factors and is expressed exclusively in cells of hematopoietic origin. The human C/EBPepsilon gene is transcribed by two alternative promoters, Palpha and Pbeta. A combination of differential splicing and al...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.12.6462
更新日期:1997-06-10 00:00:00
abstract::We describe a quantum mechanics/molecular mechanics investigation of the guanidinoacetate methyltransferase catalyzed reaction, which shows that proton transfer from guanidinoacetate (GAA) to Asp-134 and methyl transfer from S-adenosyl-L-methionine (AdoMet) to GAA are concerted. By self-consistent-charge density funct...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0607503103
更新日期:2006-10-31 00:00:00
abstract::To test whether gravity is required for normal amphibian development, Xenopus laevis females were induced to ovulate aboard the orbiting Space Shuttle. Eggs were fertilized in vitro, and although early embryonic stages showed some abnormalities, the embryos were able to regulate and produce nearly normal larvae. These...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.6.1975
更新日期:1995-03-14 00:00:00
abstract::The mouse skeletal muscle acetylcholine receptor is regulated, at least in part, by transcriptional mechanisms. As a first step toward defining the cis- and trans-acting factors involved in acetylcholine receptor transcriptional regulation, we examined mouse muscle and fibroblast cells for the presence of DNase I-hype...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.21.8405
更新日期:1986-11-01 00:00:00
abstract::All extant life employs the same 20 amino acids for protein biosynthesis. Studies on the number of amino acids necessary to produce a foldable and catalytically active polypeptide have shown that a basis set of 7-13 amino acids is sufficient to build major structural elements of modern proteins. Hence, the reasons for...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1717100115
更新日期:2018-01-02 00:00:00
abstract::Society makes substantial investments in biomedical research, searching for ways to better human health. The product of this research is principally information published in scientific journals. Continued investment in science relies on society's confidence in the accuracy, honesty, and utility of research results. A ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1504955112
更新日期:2015-09-08 00:00:00
abstract::We have previously proven that human macrophages can phagocytose porcine cells even in the absence of Ab or complement opsonization, indicating that macrophages present a pivotal immunological obstacle to xenotransplantation. A recent report indicates that the signal regulatory protein (SIRP)alpha is a critical immune...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0609661104
更新日期:2007-03-20 00:00:00
abstract::Daphnia pulex de Geer and Daphnia magna Straus populations cannot be maintained in defined (sensu stricto) media containing less than 0.1 part per billion (ppb) of selenium. A concentration of 1 ppb is sufficient to satisfy minimal needs in otherwise sufficient media. In the first generation with no selenium added to ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.11.3433
更新日期:1984-06-01 00:00:00
abstract::A variety of peptide-secreting endocrine cells contain a population of recycling microvesicles that share several major membrane polypeptides with neuronal synaptic vesicles (SVs). The function of these synaptic-like microvesicles (SLMVs) remains to be elucidated. It was previously suggested that SLMVs of pancreatic b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.11.5317
更新日期:1993-06-01 00:00:00
abstract::Faster aging is predicted in more active tissues and animals because of greater reactive oxygen species generation. Yet age-related cell loss is greater in less active cell types, such as type II muscle fibers. Mitochondrial uncoupling has been proposed as a mechanism that reduces reactive oxygen species production an...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0610131104
更新日期:2007-01-16 00:00:00
abstract::Cells contain numerous enzymes that use molecular oxygen for their reactions. Often, their active sites are buried deeply inside the protein, which raises the question whether there are specific access channels guiding oxygen to the site of catalysis. Choosing 12/15-lipoxygenase as a typical example for such oxygen-de...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0702401104
更新日期:2007-08-14 00:00:00
abstract::Vascular endothelial growth factor receptor-3 (VEGFR-3) is a major mediator of lymphangiogenesis. Recently, VEGFR-3 ligands, VEGF-C, and VEGF-D were reported to promote tumor lymphangiogenesis and lymphatic metastasis, and these processes were inhibited by blocking of the VEGFR-3-signaling pathway. Here, we have adapt...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.062040199
更新日期:2002-06-25 00:00:00
abstract::Synaptically released glutamate has been identified as a signal coupling excitatory neuronal activity to increased glucose utilization. The proposed mechanism of this coupling involves glutamate uptake into astrocytes resulting in increased intracellular Na+ (Nai+) and activation of the Na+/K+-ATPase. Increased metabo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2132096100
更新日期:2003-10-14 00:00:00
abstract::The ability of estrogens to stimulate the transcriptional activity of the estrogen receptor can be inhibited by a diverse range of estrogen antagonists. Here we show that the antiestrogen ICI 164,384, N-(n-butyl)-11-[3,17 beta-dihydroxy-estra-1,3,5(10)-trien-7 alpha-yl]N-methylundecanamide, rapidly reduces the levels ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.9.4037
更新日期:1992-05-01 00:00:00
abstract::Circulating platelets have important functions in thrombosis and in modulating immune and inflammatory responses. However, the role of platelets in innate immunity to bacterial infection is largely unexplored. While human platelets rapidly kill Staphylococcus aureus, we found the neonatal pathogen group B Streptococcu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1815572116
更新日期:2019-04-09 00:00:00
abstract::Several recombinant cowpox viruses were constructed and used to identify a viral gene that controls the production of hemorrhage in lesions caused by the Brighton Red strain of cowpox virus (CPV-BR). This gene is located in the KpnD fragment of CPV-BR DNA, between 31 and 32 kilobases from the end of the genome. This p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.20.7698
更新日期:1986-10-01 00:00:00
abstract::The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin-protein ligase that targets for degradation cell-cycle regulatory proteins during exit from mitosis and in the G1 phase of the cell cycle. The activity of APC/C in mitosis and in G1 requires interaction with the activator proteins Cdc20 and C...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0510695103
更新日期:2006-02-14 00:00:00
abstract::Mechanical signals are important influences on the development and morphology of higher plants. Using tobacco transformed with the Ca(2+)-sensitive luminescent protein aequorin, we recently reported the effects of mechanical signals of touch and wind on the luminescence and thus intracellular calcium of young seedling...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.10.4124
更新日期:1995-05-09 00:00:00
abstract::CD45, a protein tyrosine phosphatase that regulates Src family kinases, is important for regulating T cell and B cell receptor signaling; however, little is known about how CD45 regulates immunoreceptor tyrosine-based activation motif (ITAM)-dependent natural killer (NK) cell receptor signaling and the resulting effec...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0601851103
更新日期:2006-05-02 00:00:00
abstract::Serum from bacillus Calmette-Guerin-infected mice injected with endotoxin induces the appearance of surface immunoglobulin, Ia antigen, and complement receptor on the surface of precursor bone-marrow-derived (B) cells. While endotoxin itself causes phenotypic conversion of both thymus-derived (T) cells and B cells in ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.3.1200
更新日期:1977-03-01 00:00:00
abstract::Species-specific colors and patterns on animal body surfaces are determined primarily by neural-crest-derived pigment cells in the skin (chromatophores). However, even closely related species display widely differing patterns. These contrasting aspects of chromatophores (i.e., the fixed developmental control within sp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0401278101
更新日期:2004-07-20 00:00:00
abstract::Originally recognized for their role in lipoprotein metabolism and cardiovascular disease, apolipoprotein (apo) E isoforms (apoE2, apoE3, and apoE4) have also been implicated to play a key role in several biological processes not directly related to their lipid transport function. For example, apoE4 contributes signif...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0803526105
更新日期:2008-06-24 00:00:00
abstract::The planarity of peptide bonds is an assumption that underlies decades of theoretical modeling of proteins. Peptide bonds strongly deviating from planarity are considered very rare features of protein structure that occur for functional reasons. Here, empirical analyses of atomic-resolution protein structures reveal t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1107115108
更新日期:2012-01-10 00:00:00
abstract::Because of the rise in atmospheric oxygen 2.3 billion years ago (Gya) and the subsequent changes in oceanic redox state over the last 2.3-1 Gya, trace metal bioavailability in marine environments has changed dramatically. Although theorized to have influenced the biological usage of metals leaving discernable genomic ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0605798103
更新日期:2006-11-21 00:00:00
abstract::High titered IgE, IgG, and IgM antibody responses to the major antigenic determinant of penicillin, the benzylpenicilloyl hapten, were elicited by the intraperitoneal injection of the hapten coupled to keyhole limpet hemocyanin mixed with the appropriate adjuvant. However, treatment of such mice with the benzylpenicil...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.6.2091
更新日期:1976-06-01 00:00:00
abstract::We have investigated the frequency of p53 mutations in B- and T-cell human lymphoid malignancies, including acute lymphoblastic leukemia, the major subtypes of non-Hodgkin lymphoma, and chronic lymphocytic leukemia. p53 exons 5-9 were studied by using genomic DNA from 197 primary tumors and 27 cell lines by single-str...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.12.5413
更新日期:1991-06-15 00:00:00