A5073330723- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Cancer therapeutics and mechanisms
- Diagnosis and treatment of tuberculosis
- Biochemical and Molecular Research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthesis and biological activity
- Pneumocystis jirovecii pneumonia detection and treatment
- Bioactive Compounds and Antitumor Agents
- Helicobacter pylori-related gastroenterology studies
- Cancer Research and Treatments
- Computational Drug Discovery Methods
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Infectious Diseases and Tuberculosis
- Immunodeficiency and Autoimmune Disorders
- Digestive system and related health
- Eicosanoids and Hypertension Pharmacology
- ATP Synthase and ATPases Research
- CRISPR and Genetic Engineering
- Synthesis and Reactivity of Heterocycles
Centre National de la Recherche Scientifique
2018-2024
Institut Pasteur
2018-2024
Université Paris Cité
2022-2024
Comenius University Bratislava
2012-2021
Cornell University
2012
Moritz Klinik
2012
Choate Rosemary Hall
2012
MmpL3 is an inner membrane transporter of Mycobacterium tuberculosis responsible for the export trehalose momomycolate, a precursor mycobacterial outer component dimycolate (TDM), as well mycolic acids bound to arabinogalactan. represents emerging target therapy. In this paper, we describe construction and characterization mmpL3 knockdown strain M. tuberculosis. Downregulation led stop in bacterial division rapid cell death, preceded by accumulation TDM precursors. was also shown be...
Isoxyl (ISO) and thiacetazone (TAC), two prodrugs once used in the clinical treatment of tuberculosis, have long been thought to abolish Mycobacterium tuberculosis (M. tuberculosis) growth through inhibition mycolic acid biosynthesis, but their respective targets this pathway remained elusive. Here we show that treating M. with ISO or TAC results both cases accumulation 3-hydroxy C(18), C(20), C(22) fatty acids, suggestive an dehydratase step fatty-acid synthase type II elongation cycle....
A series of isoniazid derivatives bearing a phenolic or heteroaromatic coupled frame were obtained by mechanochemical means. Their pH stability and their structural (conformer/isomer) analysis checked. The activity prepared against Mycobacterium tuberculosis cell growth was evaluated. Some compounds such as hydrazine 1a almost all ones, especially 2, 5 7, are more active than isoniazid, some M. MDR clinical isolates determined. Compounds 7 present selectivity index >1400 evaluated on MRC5...
Multidrug resistant (MDR) strains of Mycobacterium tuberculosis represent an obstacle to eradicating (TB) due the low treatment success rate MDR TB. Among them, B0/W148 clone has recently evolved from M. Beijing lineage 2 and widely disseminated in Russia Europe. To get more insights into genetic factors underlying evolutionary addition environmental patient-related features, we focused on two mutations specific this that are found transcriptional regulators WhiB6 KdpDE investigated a H37Rv...
Data on the bacterial sex-mediated impact mycobacterial evolution are limited. Hence, our results presented here of importance as they clearly demonstrate capacity a wide range human- and animal-adapted Mycobacterium tuberculosis complex (MTBC) strains to transfer chromosomal DNA selected canettii .
The borderline between virulence and efficacy in live attenuated vaccine strains is often blurred this also the case for Bacillus Calmette-Guérin (BCG), only currently licensed anti-tuberculosis used on a large, global scale, which was obtained almost 100 years ago. While BCG more than 99% identical at genome level to Mycobacterium tuberculosis, causative pathogen of human some important differences factors cause naturally irreversible attenuation safety immunocompetent host. Some these are...
ABSTRACT Tuberculosis remains a major worldwide epidemic because of its sole etiological agent, Mycobacterium tuberculosis . Ethionamide (ETH) is one the antitubercular drugs used to treat infections with multidrug-resistant M. strains. ETH prodrug that requires activation within mycobacterial cell; bioactivation involves ethA-ethR locus, which encodes monooxygenase EthA, while EthR transcriptional regulator binds intergenic promoter region locus. While most studies have focused on role...
The thienopyrimidine TP053 is an antitubercular prodrug active against both replicating and nonreplicating Mycobacterium tuberculosis (M. tuberculosis) cells, which requires activation by the mycothiol-dependent nitroreductase Mrx2. investigation of mechanism action revealed that Mrx2 releases nitric oxide from this drug in enzyme assays with purified mycobacterial cultures, can explain its activity bacilli, similar to pretomanid activated Ddn. In addition, we identified a highly reactive...
The genome of the human intracellular pathogen Mycobacterium tuberculosis encodes an unusually large number epoxide hydrolases, which are thought to be involved in lipid metabolism and detoxification reactions needed endure hostile environment host macrophages. These enzymes therefore represent suitable targets for compounds such as urea derivatives, known inhibitors soluble hydrolases. In this work, we studied vitro effect thiourea drug isoxyl on six hydrolases M. using a fatty acid...
Since 2004, a tuberculosis surveillance protocol has been carried out in Aragon, thereby managing to detect all outbreaks that take place the community. The largest outbreak was caused by strain named Mycobacterium Zaragoza (MtZ), causing 242 cases as of 2020. main objective this work analyze and molecular characteristics successful could be related its greater transmission. To do this, we first applied whole-genome sequencing 57 isolates. This revealed two principal transmission clusters...
The thienopyrimidine TP053 is an antitubercular prodrug active against both replicating and non-replicating Mycobacterium tuberculosis cells. Its mechanism of activation involves the reduction a NO2 group by mycothiol-dependent reductase Mrx2, which has been hypothesized to be responsible for toxic effects in M. Similar mechanisms action have described other prodrugs containing group, such as nitroimidazoles. By multidisciplinary approach, it demonstrated that global perturbation...