Abstract：
:Streptococcus pneumoniae can cause disease in various human tissues and organs, including the ear, the brain, the blood, and the lung, and thus in highly diverse and dynamic environments. It is challenging to study how pneumococci control virulence factor expression, because cues of natural environments and the presence of an immune system are difficult to simulate in vitro. Here, we apply synthetic biology methods to reverse-engineer gene expression control in S. pneumoniae A selection platform is described that allows for straightforward identification of transcriptional regulatory elements out of combinatorial libraries. We present TetR- and LacI-regulated promoters that show expression ranges of four orders of magnitude. Based on these promoters, regulatory networks of higher complexity are assembled, such as logic AND gates and IMPLY gates. We demonstrate single-copy genome-integrated toggle switches that give rise to bimodal population distributions. The tools described here can be used to mimic complex expression patterns, such as the ones found for pneumococcal virulence factors. Indeed, we were able to rewire gene expression of the capsule operon, the main pneumococcal virulence factor, to be externally inducible (YES gate) or to act as an IMPLY gate (only expressed in absence of inducer). Importantly, we demonstrate that these synthetic gene-regulatory networks are functional in an influenza A virus superinfection murine model of pneumonia, paving the way for in vivo investigations of the importance of gene expression control on the pathogenicity of S. pneumoniae.
journal_name
Proc Natl Acad Sci U S Aauthors
Sorg RA,Gallay C,Van Maele L,Sirard JC,Veening JWdoi
10.1073/pnas.1920015117subject
Has Abstractpub_date
2020-11-03 00:00:00pages
27608-27619issue
44eissn
0027-8424issn
1091-6490pii
1920015117journal_volume
117pub_type
杂志文章abstract：:The importance of receptor binding in the potent immunogenicity of Escherichia coli heat-labile enterotoxin B subunit (EtxB) was tested by comparing its immunogical properties with those of a receptor binding mutant, EtxB(G33D). Subcutaneous immunization of EtxB(G33D) resulted in 160-fold reduction in antibody titer 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.93.1.226
更新日期：1996-01-09 00:00:00
abstract：:A fundamental issue in human development concerns how the young infant's ability to recognize emotional signals is acquired through both biological programming and learning factors. This issue is extremely difficult to investigate because of the variety of sensory experiences to which humans are exposed immediately af...
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.142165999
更新日期：2002-06-25 00:00:00
abstract：:Synucleinopathies are a group of progressive disorders characterized by the abnormal aggregation and accumulation of α-synuclein (aSyn), an abundant neuronal protein that can adopt different conformations and biological properties. Recently, aSyn pathology was shown to spread between neurons in a prion-like manner. Pr...
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.1606791113
更新日期：2016-10-18 00:00:00
abstract：:Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (Nmt1p; EC 2.3.1.97) is an essential enzyme that is highly selective for myristoyl-CoA in vivo. It is unclear why myristate (C14:0), a rare cellular fatty acid, has been selected for this covalent protein modification over more abundant fatty acids ...
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.89.21.10507
更新日期：1992-11-01 00:00:00
abstract：:The observed intensities of the reflections from the body-centered cubic phase of lipid systems are shown to be incompatible with a recently reported model consisting of straight, indefinitely long rods. ...
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.78.8.4683
更新日期：1981-08-01 00:00:00
abstract：:Since the days of Hertz, radio transmitters have evolved from rudimentary circuits emitting around 50 MHz to modern ubiquitous Wi-Fi devices operating at gigahertz radio bands. As wireless data traffic continues to increase, there is a need for new communication technologies capable of high-frequency operation for hig...
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.1903534116
更新日期：2019-05-07 00:00:00
abstract：:We provide here evidence that supports the occurrence of a biologically dormant form of selectin ligand carbohydrate, the sialyl 6-sulfo Lewis X containing modified sialic acid, in human leukocytes. The modification of sialic acid involves first de-N-acetylation of sialic acid moiety through ubiquitous de-N-acetylatio...
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.96.4.1597
更新日期：1999-02-16 00:00:00
abstract：:Tissue cultures of Actinidia kolomikta can be maintained as callus through repeated passages on a nutrient medium devoid of cytokinin but containing inorganic nutrients, sucrose, and other basal organics plus auxin. Under these conditions, actively growing callus contained 2 and 0.5 nmol of the cytokinins zeatin [io(6...
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.83.4.972
更新日期：1986-02-01 00:00:00
abstract：:In that salmonellae have been implicated in an unprecedented array of diseases, sequences found to be specific to this species are often thought to be involved in the virulence attributes not seen in other enteric bacteria. To identify the molecular, genetic, and phenotypic characteristics that differentiate bacterial...
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.90.3.1033
更新日期：1993-02-01 00:00:00
abstract：:Metabolic engineering seeks to reprogram microbial cells to efficiently and sustainably produce value-added compounds. Since chemical production can be at odds with the cell's natural objectives, strategies have been developed to balance conflicting goals. For example, dynamic regulation modulates gene expression to f...
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.1911144116
更新日期：2019-12-17 00:00:00
abstract：:Sessile marine organisms are prolific sources of biologically active natural products. However, these compounds are often found in highly variable amounts, with the abiotic and biotic factors governing their production remaining poorly understood. We present an approach that permits monitoring of in vivo natural produ...
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.1012813108
更新日期：2011-03-29 00:00:00
abstract：:The absorption spectrum of an activesite specific chromophoric acyl enzyme, sturgeon beta-(2-furyl)-acryloyl-glyceraldehyde-3-phosphate dehydrogenase, is reported. This acyl enzyme undergoes all of the catalyzed reactions characteristic of the intermediate of the physiological acyl enzyme, 3-phospho-D-glyceroyl-glycer...
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.70.7.2077
更新日期：1973-07-01 00:00:00
abstract：:The elevation of Ca2+ levels in the cytoplasm inactivates inward-rectifying K+ channels that play a central role in regulating the apertures of stomatal pores in higher plants. However, the mechanism for the Ca(2+)-mediated inhibition of K(+)-channel function is unknown. Using patch-clamp techniques, we show that cycl...
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.90.6.2202
更新日期：1993-03-15 00:00:00
abstract：:How olfactory sensory neurons converge on spatially invariant glomeruli in the olfactory bulb is largely unknown. In one model, olfactory sensory neurons interact with spatially restricted guidance cues in the bulb that orient and guide them to their target. Identifying differentially expressed molecules in the olfact...
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.0404872101
更新日期：2004-08-24 00:00:00
abstract：:Hox5 genes (Hoxa5, Hoxb5, Hoxc5) are exclusively expressed in the lung mesenchyme during embryogenesis, and the most severe phenotypes result from constitutive loss of function of all three genes. Because Hox5 triple null mutants exhibit perinatal lethality, the contribution of this paralogous group to postembryonic l...
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.1807067115
更新日期：2018-11-06 00:00:00
abstract：:Cdc10-dependent transcript 1 (Cdt1) is an essential DNA replication protein whose accumulation at the end of the cell cycle promotes the formation of pre-replicative complexes and replication in the next cell cycle. Geminin is thought to be involved in licensing replication by promoting the accumulation of Cdt1 in mit...
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.1310677110
更新日期：2013-07-23 00:00:00
abstract：:Prenatal stress exposure is associated with risk for psychiatric disorders later in life. This may be mediated in part via enhanced exposure to glucocorticoids (GCs), which are known to impact neurogenesis. We aimed to identify molecular mediators of these effects, focusing on long-lasting epigenetic changes. In a hum...
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.1820842116
更新日期：2020-09-22 00:00:00
abstract：:Niemann-Pick C1 (NPC1) and NPC2 proteins are indispensable for the export of LDL-derived cholesterol from late endosomes. Mutations in these proteins result in Niemann-Pick type C disease, a lysosomal storage disease. Despite recent reports of the NPC1 structure depicting its overall architecture, the function of its ...
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.1711716114
更新日期：2017-08-22 00:00:00
abstract：:Hypertension increases the pressure load on the heart and is associated with a poorly understood chronic systemic inflammatory state. Interleukin 33 (IL-33) binds to membrane-bound ST2 (ST2L) and has antihypertrophic and antifibrotic effects in the myocardium. In contrast, soluble ST2 appears to act as a decoy recepto...
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.1424236112
更新日期：2015-06-09 00:00:00
abstract：:Growth inhibition assays indicated that the IC50 values for methotrexate (MTX) and 5-fluorodeoxyuridine (FdUrd) in HS-18, a liposarcoma cell line lacking retinoblastoma protein (pRB), and SaOS-2, an osteosarcoma cell line with a truncated and nonfunctional pRB, were 10- to 12-fold and 4- to 11-fold higher, respectivel...
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.92.22.10436
更新日期：1995-10-24 00:00:00
abstract：:Brief learning experience (classical conditioning) induces frequency-specific receptive-field (RF) plasticity in the auditory cortex, characterized as increased response to the frequency of the conditioned stimulus and decreased responses to most other frequencies, including the pretraining best frequency. This experi...
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.90.6.2394
更新日期：1993-03-15 00:00:00
abstract：:Rod signals in the mammalian retina are thought to reach ganglion cells over the circuit rod-->rod depolarizing bipolar cell-->AII amacrine cell-->cone bipolar cells-->ganglion cells. A possible alternative pathway involves gap junctions linking the rods and cones, the circuit being rod-->cone-->cone bipolar cells-->g...
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.92.23.10658
更新日期：1995-11-07 00:00:00
abstract：:The ribonucleotide reductase system of Escherichia coli B participates in the biosynthesis of DNA by reducing ribonucleoside diphosphates to the corresponding deoxyribonucleotides. The enzyme is regulated in a complicated way by allosteric modifiers. We now find that infection of E. coli with the bacteriophage T4 resu...
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.62.3.829
更新日期：1969-03-01 00:00:00
abstract：:A light beam hitting the retina produces an excitatory process; however, around the edge of the light beam, sensory cells are inhibited and lose their sensitivity. This combination of stimulation and inhibition produces a discrepancy between the luminance pattern presented to the eye and the brightness pattern that is...
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.69.4.885
更新日期：1972-04-01 00:00:00
abstract：:To address the significance of human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cells (PBMCs), we have used reverse transcriptase-initiated PCR to measure HIV-1 mRNA expression in PBMC specimens collected from a cohort of HIV-infected individuals during a long-term prospective study. We f...
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.91.3.1104
更新日期：1994-02-01 00:00:00
abstract：:The basic biochemical mechanisms underlying many heritable human polycystic diseases are unknown despite evidence that most cases are caused by mutations in members of several protein families, the most prominent being the polycystin gene family, whose products are found on the primary cilia, or due to mutations in po...
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.0700908104
更新日期：2007-05-29 00:00:00
abstract：:Polymorphism in materials often leads to significantly different physical properties--the rutile and anatase polymorphs of TiO2 are a prime example. Polytypism is a special type of polymorphism, occurring in layered materials when the geometry of a repeating structural layer is maintained but the layer-stacking sequen...
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.1502460112
更新日期：2015-03-17 00:00:00
abstract：:We explored the feasibility of designing retroviral vectors that can target human breast cancer cells with characteristic receptors via ligand-receptor interaction. The ecotropic Moloney murine leukemia virus envelope was modified by insertion of sequences encoding human heregulin. Ecotropic virus, which normally does...
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.92.21.9747
更新日期：1995-10-10 00:00:00
abstract：:Development of type 1 diabetes in the nonobese diabetic (NOD) mouse is preceded by an immune cell infiltrate in the pancreatic islets. The exact role of the attracted cells is still poorly understood. Chemokine CCL2/MCP-1 is known to attract CCR2(+) monocytes and dendritic cells (DCs). We have previously shown that tr...
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.1115308109
更新日期：2012-02-28 00:00:00
abstract：:Agrobacterium tumefaciens can transfer part of its Ti plasmid, the T-DNA, to plant cells where it integrates into the nuclear genome via illegitimate recombination. Integration of the T-DNA results in small deletions of the plant target DNA, and may lead to truncation of the T-DNA borders and the production of filler ...
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.93.26.15272
更新日期：1996-12-24 00:00:00
