Mycobacterium tuberculosis virulence inhibitors discovered by Mycobacterium marinum high-throughput screening.

Abstract:

:High-throughput screening facilities do not generally support biosafety level 3 organisms such as Mycobacterium tuberculosis. To discover not only antibacterials, but also virulence inhibitors with either bacterial or host cell targets, an assay monitoring lung fibroblast survival upon infection was developed and optimized for 384-plate format and robotic liquid handling. By using Mycobacterium marinum as surrogate organism, 28,000 compounds were screened at biosafety level 2 classification, resulting in 49 primary hits. Exclusion of substances with unfavourable properties and known antimicrobials resulted in 11 validated hits of which 7 had virulence inhibiting properties and one had bactericidal effect also in wild type Mycobacterium tuberculosis. This strategy to discover virulence inhibitors using a model organism in high-throughput screening can be a valuable tool for other researchers working on drug discovery against tuberculosis and other biosafety level 3 infectious agents.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Tükenmez H,Edström I,Ummanni R,Fick SB,Sundin C,Elofsson M,Larsson C

doi

10.1038/s41598-018-37176-4

subject

Has Abstract

pub_date

2019-01-10 00:00:00

pages

26

issue

1

issn

2045-2322

pii

10.1038/s41598-018-37176-4

journal_volume

9

pub_type

杂志文章
  • Synthesis of two-dimensional Tl(x)Bi(1-x) compounds and Archimedean encoding of their atomic structure.

    abstract::Crystalline atomic layers on solid surfaces are composed of a single building block, unit cell, that is copied and stacked together to form the entire two-dimensional crystal structure. However, it appears that this is not an unique possibility. We report here on synthesis and characterization of the one-atomic-layer-...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep19446

    authors: Gruznev DV,Bondarenko LV,Matetskiy AV,Mihalyuk AN,Tupchaya AY,Utas OA,Eremeev SV,Hsing CR,Chou JP,Wei CM,Zotov AV,Saranin AA

    更新日期:2016-01-19 00:00:00

  • Energy metabolism in intestinal epithelial cells during maturation along the crypt-villus axis.

    abstract::Intestinal epithelial cells continuously migrate and mature along crypt-villus axis (CVA), while the changes in energy metabolism during maturation are unclear in neonates. The present study was conducted to test the hypothesis that the energy metabolism in intestinal epithelial cells would be changed during maturatio...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep31917

    authors: Yang H,Wang X,Xiong X,Yin Y

    更新日期:2016-08-25 00:00:00

  • Epitope mapping of diverse influenza Hemagglutinin drug candidates using HDX-MS.

    abstract::Epitope characterization is critical for elucidating the mechanism of action of drug candidates. However, traditional high-resolution epitope mapping techniques are not well suited for screening numerous drug candidates recognizing a similar target. Here, we use Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS) t...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-41179-0

    authors: Puchades C,Kűkrer B,Diefenbach O,Sneekes-Vriese E,Juraszek J,Koudstaal W,Apetri A

    更新日期:2019-03-18 00:00:00

  • Polyphenols (S3) Isolated from Cone Scales of Pinus koraiensis Alleviate Decreased Bone Formation in Rat under Simulated Microgravity.

    abstract::In order to screen out an effective bone loss protectant from natural plant polyphenol and to elucidate the mechanism of the plant polyphenols that alleviate bone loss under simulated microgravity, the proliferation activities of 9 total polyphenol extracts from natural product (TPENP) on osteoblasts were measured. Po...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-30992-8

    authors: Diao Y,Chen B,Wei L,Wang Z

    更新日期:2018-08-24 00:00:00

  • Effect of selected biocides on microbiologically influenced corrosion caused by Desulfovibrio ferrophilus IS5.

    abstract::The marine bacterial strain Desulfovibrio ferrophilus IS5, known for its lithotrophic growth ability to use metallic iron as a sole electron donor and for causing corrosion of steel, was used in the current study. Four commonly used biocides in the oil and gas industry, namely tetrakis(hydroxymethyl) phosphonium sulfa...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-34789-7

    authors: Sharma M,Liu H,Chen S,Cheng F,Voordouw G,Gieg L

    更新日期:2018-11-09 00:00:00

  • Localized Down-regulation of P-glycoprotein by Focused Ultrasound and Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain.

    abstract::Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep31201

    authors: Cho H,Lee HY,Han M,Choi JR,Ahn S,Lee T,Chang Y,Park J

    更新日期:2016-08-11 00:00:00

  • Elevated Serum Interleukin-34 Level in Patients with Systemic Lupus Erythematosus Is Associated with Disease Activity.

    abstract::We measured the interleukin-34 (IL-34) level in sera from patients with systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) using an enzyme-linked immunosorbent assay (ELISA). Blood tests, including assays to determine C-reactive protein (CRP), complement (C) 3, C4, immunoglobulin (Ig) A, IgG, IgM...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-21859-z

    authors: Xie HH,Shen H,Zhang L,Cui MY,Xia LP,Lu J

    更新日期:2018-02-22 00:00:00

  • Genome-wide CRISPR Screen to Identify Genes that Suppress Transformation in the Presence of Endogenous KrasG12D.

    abstract::Cooperating gene mutations are typically required to transform normal cells enabling growth in soft agar or in immunodeficient mice. For example, mutations in Kras and transformation-related protein 53 (Trp53) are known to transform a variety of mesenchymal and epithelial cells in vitro and in vivo. Identifying other ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-53572-w

    authors: Huang J,Chen M,Xu ES,Luo L,Ma Y,Huang W,Floyd W,Klann TS,Kim SY,Gersbach CA,Cardona DM,Kirsch DG

    更新日期:2019-11-20 00:00:00

  • Brain wave classification using long short-term memory network based OPTICAL predictor.

    abstract::Brain-computer interface (BCI) systems having the ability to classify brain waves with greater accuracy are highly desirable. To this end, a number of techniques have been proposed aiming to be able to classify brain waves with high accuracy. However, the ability to classify brain waves and its implementation in real-...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-45605-1

    authors: Kumar S,Sharma A,Tsunoda T

    更新日期:2019-06-24 00:00:00

  • Characteristics of Cadmium Sorption by Heat-Activated Red Mud in Aqueous Solution.

    abstract::Red mud as a waste material is produced in large quantities by the aluminum industry. Heat activation has been used to enhance sorption capacity of red mud for its beneficial reuse as an effective sorbent. In this study, heat-activated red mud (HARM) was investigated for its Cd(II) sorption capacity under various proc...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-31967-5

    authors: Yang T,Sheng L,Wang Y,Wyckoff KN,He C,He Q

    更新日期:2018-09-10 00:00:00

  • The Traditional Chinese Medicine MLC901 inhibits inflammation processes after focal cerebral ischemia.

    abstract::Inflammation is considered as a major contributor to brain injury following cerebral ischemia. The therapeutic potential of both MLC601/MLC901, which are herbal extract preparations derived from Chinese Medicine, has been reported both in advanced stroke clinical trials and also in animal and cellular models. The aim ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-36138-0

    authors: Widmann C,Gandin C,Petit-Paitel A,Lazdunski M,Heurteaux C

    更新日期:2018-12-24 00:00:00

  • Ecological responses to flow variation inform river dolphin conservation.

    abstract::Many environmental flow (e-flow) studies and applications have predominantly used state-(i.e., at a single time point) and rate-(i.e., temporal change) based demographic characteristics of species representing lower trophic levels (e.g., fish communities) to build flow-ecology relationships, rather than using a proces...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-79532-3

    authors: Paudel S,Koprowski JL,Thakuri U,Sigdel R,Gautam RC

    更新日期:2020-12-18 00:00:00

  • Balancing Speed and Coverage by Sequential Seeding in Complex Networks.

    abstract::Information spreading in complex networks is often modeled as diffusing information with certain probability from nodes that possess it to their neighbors that do not. Information cascades are triggered when the activation of a set of initial nodes - seeds - results in diffusion to large number of nodes. Here, several...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-00937-8

    authors: Jankowski J,Bródka P,Kazienko P,Szymanski BK,Michalski R,Kajdanowicz T

    更新日期:2017-04-18 00:00:00

  • Honeybee pupal length assessed by CT-scan technique: effects of Varroa infestation, developmental stage and spatial position within the brood comb.

    abstract::Honeybee pupae morphology can be affected by a number of stressor, but in vivo investigation is difficult. A computed tomography (CT) technique was applied to visualize a comb's inner structure without damaging the brood. The CT scan was performed on a brood comb containing pupae developed from eggs laid by the queen ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-46474-4

    authors: Facchini E,Nalon L,Andreis ME,Di Giancamillo M,Rizzi R,Mortarino M

    更新日期:2019-07-23 00:00:00

  • Vitamin D deficiency, cardiothoracic ratio, and long-term mortality in hemodialysis patients.

    abstract::Hemodialysis patients are a special group of patients with higher mortality rates. Hemodialysis patients with vitamin D deficiency {plasma levels of 25-hydroxyvitamin D [25(OH)D] below 20 ng/mL} are associated with even higher mortality rates. The prognostic importance of vitamin D deficiency in hemodialysis patients ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-64359-9

    authors: Hsu HJ,Wu IW,Hsu KH,Sun CY,Chen CY,Lee CC

    更新日期:2020-05-05 00:00:00

  • A Miocene impact ejecta layer in the pelagic Pacific Ocean.

    abstract::Meteorite impacts have caused catastrophic perturbations to the global environment and mass extinctions throughout the Earth's history. Here, we present petrographic and geochemical evidence of a possible impact ejecta layer, dating from about 11 Ma, in deep-sea clayey sediment in the Northwest Pacific. This clay laye...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-52709-1

    authors: Nozaki T,Ohta J,Noguchi T,Sato H,Ishikawa A,Takaya Y,Kimura JI,Chang Q,Shimada K,Ishibashi JI,Yasukawa K,Kimoto K,Iijima K,Kato Y

    更新日期:2019-11-20 00:00:00

  • Vibrational communication between a myrmecophilous butterfly Spindasis lohita (Lepidoptera: Lycaenidae) and its host ant Crematogaster rogenhoferi (Hymenoptera: Formicidae).

    abstract::Ants are a dominant insect group in terrestrial ecosystems and many myrmecophilous species evolve to associate with ants to gain benefits. One iconic example is myrmecophilous butterflies that often produce ant-mimicking vibrational calls to modulate ant behaviors. Despite its popularity, empirical exploration of how ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-54966-6

    authors: Lin YH,Liao YC,Yang CS,Billen J,Yang MM,Hsu YF

    更新日期:2019-12-06 00:00:00

  • In vitro and in vivo host range of Anopheles gambiae densovirus (AgDNV).

    abstract::AgDNV is a powerful gene transduction tool and potential biological control agent for Anopheles mosquitoes. Using a GFP reporter virus system, we investigated AgDNV host range specificity in four arthropod cell lines (derived from An. gambiae, Aedes albopictus and Drosophila melanogaster) and six mosquito species from...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep12701

    authors: Suzuki Y,Barik TK,Johnson RM,Rasgon JL

    更新日期:2015-07-29 00:00:00

  • Effect of gallic acid on the larvae of Spodoptera litura and its parasitoid Bracon hebetor.

    abstract::The antibiosis effect of gallic acid on Spodoptera litura F. (Lepidoptera: Noctuidae) and its parasitoid evaluated by feeding six days old larvae on artificial diet incorporated with different concentrations (5 ppm, 25 ppm, 125 ppm, 625 ppm, 3125 ppm) of the phenolic compound revealed higher concentration (LC50) of ga...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-80232-1

    authors: Punia A,Chauhan NS,Singh D,Kesavan AK,Kaur S,Sohal SK

    更新日期:2021-01-12 00:00:00

  • Tracking COVID-19 using taste and smell loss Google searches is not a reliable strategy.

    abstract::Web search tools are widely used by the general public to obtain health-related information, and analysis of search data is often suggested for public health monitoring. We analyzed popularity of searches related to smell loss and taste loss, recently listed as symptoms of COVID-19. Searches on sight loss and hearing ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-77316-3

    authors: Asseo K,Fierro F,Slavutsky Y,Frasnelli J,Niv MY

    更新日期:2020-11-25 00:00:00

  • Quantum magnetism in strongly interacting one-dimensional spinor Bose systems.

    abstract::Strongly interacting one-dimensional quantum systems often behave in a manner that is distinctly different from their higher-dimensional counterparts. When a particle attempts to move in a one-dimensional environment it will unavoidably have to interact and 'push' other particles in order to execute a pattern of motio...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep10675

    authors: Dehkharghani A,Volosniev A,Lindgren J,Rotureau J,Forssén C,Fedorov D,Jensen A,Zinner N

    更新日期:2015-06-15 00:00:00

  • Mixture toxicity assisting the design of eco-friendlier plant protection products: a case-study using a commercial herbicide combining nicosulfuron and terbuthylazine.

    abstract::The development of environmentally friendly plant protection products (PPPs), including pesticides, is a challenge nowadays. A commercial herbicide combining terbuthylazine and nicosulfuron as active substances (a.s.) was selected as a model PPP. The suitability of manipulating the ratio between a.s. towards alternati...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-23883-5

    authors: Queirós L,Vidal T,Nogueira AJA,Gonçalves FJM,Pereira JL

    更新日期:2018-04-03 00:00:00

  • Neuroprotection mediated by cystatin C-loaded extracellular vesicles.

    abstract::Cystatin C (CysC) is implicated in neuroprotection and repair in the nervous system in response to diverse neurotoxic conditions. In addition to being secreted from cells in a soluble form, CysC is released by cells in association with extracellular vesicles (EVs), including exosomes. We demonstrate that EVs containin...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-47524-7

    authors: Pérez-González R,Sahoo S,Gauthier SA,Kim Y,Li M,Kumar A,Pawlik M,Benussi L,Ghidoni R,Levy E

    更新日期:2019-07-31 00:00:00

  • Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection.

    abstract::Genome editing via CRISPR/Cas9 has become an efficient and reliable way to make precise, targeted changes to the genome of living cells. CXCR4 is a co-receptor for the human immunodeficiency virus type 1 (HIV-1) infection and has been considered as an important therapeutic target for AIDS. CXCR4 mediates viral entry i...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep15577

    authors: Hou P,Chen S,Wang S,Yu X,Chen Y,Jiang M,Zhuang K,Ho W,Hou W,Huang J,Guo D

    更新日期:2015-10-20 00:00:00

  • DNA supercoiling, a critical signal regulating the basal expression of the lac operon in Escherichia coli.

    abstract::Escherichia coli lac repressor (LacI) is a paradigmatic transcriptional factor that controls the expression of lacZYA in the lac operon. This tetrameric protein specifically binds to the O1, O2 and O3 operators of the lac operon and forms a DNA loop to repress transcription from the adjacent lac promoter. In this arti...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep19243

    authors: Fulcrand G,Dages S,Zhi X,Chapagain P,Gerstman BS,Dunlap D,Leng F

    更新日期:2016-01-14 00:00:00

  • Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats.

    abstract::Aditoprim (ADP) is a newly developed antibacterial agent in veterinary medicine. The metabolism and disposition of ADP in swine, broilers, carp and rats were investigated by using a radio tracer method combined with a radioactivity detector and a liquid chromatography/ion trap/time-of-flight mass spectrometry. After a...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep20370

    authors: Wang L,Huang L,Pan Y,Kuča K,Klímová B,Wu Q,Xie S,Ahmad I,Chen D,Tao Y,Wan D,Liu Z,Yuan Z

    更新日期:2016-02-03 00:00:00

  • Chloroquine as a promising adjuvant therapy for type 1 Diabetes Mellitus.

    abstract::Chloroquine (CQ) and hydroxychloroquine, are promising anti-inflammatory drugs for the treatment of Diabetes mellitus (DM) to prevent associated complications. Therefore, this study evaluated the anti-inflammatory effects of CQ-free and CQ-incorporated polylactic acid nanoparticles (NPs) in the peripheral blood mononu...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-69001-2

    authors: de Almeida Júnior RF,de Souza KSC,Galdino OA,da Silva Junior AA,Arrais RF,Machado PRL,Farias KJS,de Rezende AA

    更新日期:2020-07-21 00:00:00

  • The reunion of two lineages of the Neotropical brown stink bug on soybean lands in the heart of Brazil.

    abstract::The rapid pace of conversion of natural areas to agricultural systems is highly concerning, and the consequences for conservation and pest management are not yet fully understood. We examined mitochondrial (COI and Cytb) and nuclear (ITS1) gene regions of 21 populations of the stink bug Euschistus heros, to investigat...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-20187-6

    authors: Soares PL,Cordeiro EMG,Santos FNS,Omoto C,Correa AS

    更新日期:2018-02-06 00:00:00

  • Low palaeoelevation of the northern Lhasa terrane during late Eocene: Fossil foraminifera and stable isotope evidence from the Gerze Basin.

    abstract::The Lhasa terrane is a key region for understanding the paleoelevation of the southern Tibetan Plateau after India-Asia collision. The Gerze Basin, located in the northern part of the Lhasa terrane, is a shortening-related basin. We discovered Lagena laevis (Bandy) fossils in upper Eocene strata of the Gerze Basin. Th...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep27508

    authors: Wei Y,Zhang K,Garzione CN,Xu Y,Song B,Ji J

    更新日期:2016-06-08 00:00:00

  • New Formyl Phloroglucinol Meroterpenoids from the Leaves of Eucalyptus robusta.

    abstract::Seven new formyl phloroglucinol meroterpenoids (FPMs), namely eucalrobusones J-P (1-7), as well as three known ones (8-10) were isolated from the leaves of Eucalyptus robusta. Their structures were elucidated by spectroscopic data analysis, and their absolute configurations were determined by applications of the Snatz...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep39815

    authors: Shang ZC,Yang MH,Liu RH,Wang XB,Kong LY

    更新日期:2016-12-22 00:00:00