Abstract:
:Mycobacterium tuberculosis, the etiological agent of the infectious disease tuberculosis, kills approximately 1.5 million people annually, while the spread of multidrug-resistant strains is of great global concern. Thus, continuous efforts to identify new antitubercular drugs as well as novel targets are crucial. Recently, two prodrugs activated by the monooxygenase EthA, 7947882 and 7904688, which target the CTP synthetase PyrG, were identified and characterized. In this work, microbiological, biochemical, and in silico methodologies were used to demonstrate that both prodrugs possess a second target, the pantothenate kinase PanK. This enzyme is involved in coenzyme A biosynthesis, an essential pathway for M. tuberculosis growth. Moreover, compound 11426026, the active metabolite of 7947882, was demonstrated to directly inhibit PanK, as well. In an independent screen of a compound library against PyrG, two additional inhibitors were also found to be active against PanK. In conclusion, these direct PyrG and PanK inhibitors can be considered as leads for multitarget antitubercular drugs and these two enzymes could be employed as a "double-tool" in order to find additional hit compounds.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Chiarelli LR,Mori G,Orena BS,Esposito M,Lane T,de Jesus Lopes Ribeiro AL,Degiacomi G,Zemanová J,Szádocka S,Huszár S,Palčeková Z,Manfredi M,Gosetti F,Lelièvre J,Ballell L,Kazakova E,Makarov V,Marengo E,Mikusova K,Coldoi
10.1038/s41598-018-21614-4subject
Has Abstractpub_date
2018-02-16 00:00:00pages
3187issue
1issn
2045-2322pii
10.1038/s41598-018-21614-4journal_volume
8pub_type
杂志文章abstract::MicroRNAs (miRNAs) are important post-transcriptional regulators involved in animal adipogenesis, however, their roles in bovine fat deposition remain poorly understood. In the present study, we conducted a comparative RNA sequencing to identify the key miRNAs involved in beef lipid accumulation by comparing the backf...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep44026
更新日期:2017-03-08 00:00:00
abstract::Infants' sensitivity to selectively attend to human speech and to process it in a unique way has been widely reported in the past. However, in order to successfully acquire language, one should also understand that speech is a referential, and that words can stand for other entities in the world. While there has been ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep13594
更新日期:2015-09-01 00:00:00
abstract::In this study, 44 compounds in the petroleum ether extract of Maqian (Zanthoxylum myriacanthum var. pubescens) bark, a traditional Dai herbal medicine, were identified by GC-MS. Major components included 3(2H)-benzofuranone, asarinin and (dimethoxymethyl)-3-methoxy-benzene. A total of 18 compounds were isolated from t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep45805
更新日期:2017-04-06 00:00:00
abstract::Cucumber is an agriculturally and economically important vegetable crop worldwide. Fruit flesh thickness is an important trait for cucumber and also a central determinant of yield, yet little is known about the underlying mechanism of this trait. In this study, bulked segregant analysis (BSA) combined with specific le...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep15829
更新日期:2015-10-28 00:00:00
abstract::An obstacle for precision improvement in quantum metrology is the information loss causing by the unavoidable interaction between probe system and environment. Quantum fluctuations are environment no system can be isolated from and it will make the precision of initial parameter estimation of the probe atom decrease w...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-00544-7
更新日期:2017-03-24 00:00:00
abstract::Small for gestational age (SGA) newborns are often born from hypertensive pregnancies. This study aimed to compare the systemic metabolism of cortisol (F) in pregnancies with SGA and appropriate for gestational age (AGA) infants, considering both the normotensive (NT) and hypertensive patients. We hypothesized that th...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-54362-0
更新日期:2019-11-29 00:00:00
abstract::Combining spectral imaging with compressive sensing (CS) enables efficient data acquisition by fully utilizing the intrinsic redundancies in natural images. Current compressive multispectral imagers, which are mostly based on array sensors (e.g, CCD or CMOS), suffer from limited spectral range and relatively low photo...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep41435
更新日期:2017-01-27 00:00:00
abstract::We report on a wavelet based space-scale decomposition method for analyzing the response of living muscle precursor cells (C2C12 myoblasts and myotubes) upon sharp indentation with an AFM cantilever and quantifying their aptitude to sustain such a local shear strain. Beyond global mechanical parameters which are curre...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-26797-4
更新日期:2018-06-05 00:00:00
abstract::In Duchenne muscular dystrophy, progressive loss of muscle tissue is accompanied by fibrosis, chronic inflammation and reduced muscle regenerative capacity. Although much is known about the development of fibrosis and chronic inflammation in muscular dystrophy, less is known about how they are mechanistically linked t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep24708
更新日期:2016-05-31 00:00:00
abstract::The observation and analysis of dendritic spines morphological changes poses a major challenge in neuroscience studies. The alterations of their density and/or morphology are indicators of the cellular processes involved in neural plasticity underlying learning and memory, and are symptomatic in neuropsychiatric disor...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-21753-8
更新日期:2018-02-23 00:00:00
abstract::Horizontal gene transfer (HGT) is a main mechanism of bacterial evolution endowing bacteria with new genetic traits. The transfer of mobile genetic elements such as plasmids (conjugation) requires the close proximity of cells. HGT between genetically distinct bacteria largely depends on cell movement in water films, w...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep36390
更新日期:2016-11-04 00:00:00
abstract::Concerted evolution is often observed in multigene families such as the CEA gene family. As a result, sequence similarity of paralogous genes is significantly higher than expected from their evolutionary distance. Gene conversion, a "copy paste" DNA repair mechanism that transfers sequences from one gene to another an...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-60425-4
更新日期:2020-02-25 00:00:00
abstract::Maximal rate of heart rate (HR) increase (rHRI) as a measure of HR acceleration during the transition from rest to exercise, or during an increase in workload, tracks exercise performance. rHRI assessed at relative rather than absolute workloads may track performance better, and a field test would increase applicabili...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-71597-4
更新日期:2020-09-03 00:00:00
abstract::Biochemical remission after transsphenoidal surgery is still unsatisfied in acromegaly patients with macroadenomas, especially with invasive macroadenomas. Concerning the impact of preoperative somatostatin analogues (SSAs) on surgical outcomes, previous studies with limited cases reported conflicting results. To asse...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析
doi:10.1038/s41598-019-50639-6
更新日期:2019-10-01 00:00:00
abstract::Change in body composition with skeletal muscle wasting, a major component of pulmonary cachexia, is associated with mortality in chronic obstructive pulmonary disease and cancer. However, its relevance in interstitial lung diseases (ILDs) remains unclear. We hypothesized changes in body composition would be associate...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-32478-z
更新日期:2018-09-19 00:00:00
abstract::FcRn mediates recycling and transcytosis of IgG and albumin in various cell types. The MHC-class-I-like protein of the FcRn heterodimer is encoded by FCGRT. Few determinants of variable FCGRT expression in humans have been identified so far. In this study, we investigated the presence of DNA methylation in regulatory ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-45203-1
更新日期:2019-06-17 00:00:00
abstract::Nutrient inputs and ultraviolet radiation (UVR) are global factors affecting the structure and functioning of aquatic ecosystems, particularly clear-water ecosystems. We performed experiments in two model lakes highly exposed to UVR fluxes in order to test the effect that future increases in mineral nutrients transpor...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-06279-9
更新日期:2017-07-24 00:00:00
abstract::Transparent Er3+-doped germanotellurite glass ceramics (GCs) with variable Te/Ge ratio were prepared by controllable heat-treated process. X-ray diffraction (XRD) and transmission electron microscope (TEM) confirmed the formation of nanocrystals in glass matrix. Raman spectra were used to investigate the evolution of ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep43186
更新日期:2017-03-07 00:00:00
abstract::The biological function of multiple repetitions of single amino acids, or homo-repeats, is largely unknown, but their occurrence in proteins has been associated with more than 20 hereditary diseases. Analysing 122 bacterial and eukaryotic genomes, we observed that the number of proteins containing homo-repeats is sign...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep26941
更新日期:2016-06-03 00:00:00
abstract::MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syn...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-58400-0
更新日期:2020-01-29 00:00:00
abstract::With the objective to conceive a plasmonic solar cell with enhanced photocurrent, we investigate the role of plasmonic nanoshells, embedded within a ultrathin microcrystalline silicon solar cell, in enhancing broadband light trapping capability of the cell and, at the same time, to reduce the parasitic loss. The thick...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep24539
更新日期:2016-04-15 00:00:00
abstract::Cellular reprogramming involves profound alterations in genome-wide gene expression that is precisely controlled by a hypothetical epigenetic code. Small molecules have been shown to artificially induce epigenetic modifications in a sequence independent manner. Recently, we showed that specific DNA binding hairpin pyr...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep00544
更新日期:2012-01-01 00:00:00
abstract::In recent years artificial neural networks achieved performance close to or better than humans in several domains: tasks that were previously human prerogatives, such as language processing, have witnessed remarkable improvements in state of the art models. One advantage of this technological boost is to facilitate co...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-79127-y
更新日期:2020-12-17 00:00:00
abstract::Pericytes regulate vessel stability and pericyte dysfunction contributes to retinopathies, stroke, and cancer. Here we define Notch as a key regulator of pericyte function during angiogenesis. In Notch1(+/-); Notch3(-/-) mice, combined deficiency of Notch1 and Notch3 altered pericyte interaction with the endothelium a...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep16449
更新日期:2015-11-13 00:00:00
abstract::We formerly developed an automatic colony count system based on the time-lapse shadow image analysis (TSIA). Here this system has been upgraded and applied to practical rapid decision. A microbial sample was spread on/in an agar plate with 90 mm in diameter as homogeneously as possible. We could obtain the results wit...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep10061
更新日期:2015-05-15 00:00:00
abstract::For N indistinguishable bosons or fermions impinged on a M-port Haar-random unitary network the average probability to count n 1, … n r particles in a small number r ≪ N of binned-together output ports takes a Gaussian form as N ≫ 1. The discovered Gaussian asymptotic law is the well-known asymptotic law for distingui...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-00044-8
更新日期:2017-02-16 00:00:00
abstract::The concept of multiscale architectured materials is established using composition and grain size gradients. Composition-gradient nanostructured materials are produced from coarse grained interstitial free steels via carburization and high-pressure torsion. Quantitative analyses of the dislocation density using X-ray ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep26590
更新日期:2016-05-27 00:00:00
abstract::O antigen (O-Ag) in many bacteria is synthesized via the Wzx/Wzy-dependent pathway in which Wzy polymerizes lipid-linked O-Ag subunits to modal lengths regulated by Wzz. Characterization of 83 site-directed mutants of Wzy from Pseudomonas aeruginosa PAO1 (WzyPa) in topologically-mapped periplasmic (PL) and cytoplasmic...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep03441
更新日期:2013-12-06 00:00:00
abstract::The evaporation of seawater in arid climates is currently the main accepted driving mechanism for the formation of ancient and recent salt deposits in shallow basins. However, the deposition of huge amounts of marine salts, including the formation of tens of metres of highly soluble types (tachyhydrite and bischofite)...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-48138-9
更新日期:2019-08-12 00:00:00
abstract::Whale shark (Rhincodon typus) tourism is increasingly popular at predictable aggregations around the world, but only a few use provisioning to ensure close interactions. Understanding the effects of provisioning on the behaviour of this endangered species is critical to manage this growing industry. We recorded the di...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-73416-2
更新日期:2020-10-12 00:00:00