A multitarget approach to drug discovery inhibiting Mycobacterium tuberculosis PyrG and PanK

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Mycobacterium Tuberculosis is a highly effective pathogen infecting nearly a third of the world's population. An M. tuberculosis infection starts when droplets containing bacteria enter an individual's lungs. The first host cells to contact the bacteria ar ...

A DNA damage-inducible mutagenic gene cassette has been implicated in the emergence of drug resistance in Mycobacterium tuberculosis during anti-tuberculosis (TB) chemotherapy. However, the molecular composition and operation of the encoded 'mycobacterial ...

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we ...

Mycobacterium tuberculosis infection is initiated by the inhalation and implantation of bacteria in the lung alveoli, where they are phagocytosed by macrophages. Even a single bacterium may be sufficient to initiate infection. Thereafter, the clinical outc ...

Protein-protein interactions (PPIs) play important roles in many diseases and their modulation is an attractive strategy for developing new therapeutics. However, the relatively large and often flat binding surfaces of PPIs makes the development of inhibit ...

The discovery of a drug requires over a decade of intensive research and financial investments – and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied ...

Propagation of microorganisms is based on three fundamental processes: cell growth, DNA replication, and cell division. Although important for antibacterial drug development, these processes are poorly understood in Actinobacteria, a medically important ph ...

Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is the world's leading cause of death from an infectious disease. One of the main features of this pathogen is the complex and dynamic lipid composition of the cell envelope, which adap ...

A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond foun ...

Mycobacterium tuberculosis is a slow-growing intracellular bacterium with the ability to induce host cell death and persist indefinitely in the human body. This pathogen uses the specialized ESX-1 secretion system to secrete virulence factors and potent im ...

The EspB protein of Mycobacterium tuberculosis is a 60 kDa virulence factor, implicated in conjugation and exported by the ESX-1 system of which it may also be a component. Previous attempts to obtain high-resolution maps of EspB by cryo-electron microscop ...

The emergence of multi-drug (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB) is a major threat to the global management of tuberculosis (TB) worldwide. New chemical entities are of need to treat drug-resistant TB. In this study, the mode of ac ...

Mycobacterium tuberculosis, the etiological agent for the tuberculosis disease, is a bacterial pathogen thought to infect about a quarter of the global human population. It is the first cause of death among infectious diseases, and is most prevalent in low ...

Macrocycles provide an attractive modality for drug development, but generating ligands for new targets is hampered by the limited availability of large macrocycle libraries. We have established a solution-phase macrocycle synthesis strategy in which three ...

Clonal microbial populations are inherently heterogeneous, and this diversification is often considered as an adaptation strategy. In clinical infections, phenotypic diversity is found to be associated with drug tolerance, which in turn could evolve into g ...

Worldwide, tuberculosis (TB) is the leading cause of death due to infection with a single pathogenic agent, Mycobacterium tuberculosis. In the absence of an effective vaccine, new, more powerful antibiotics are required to halt the growing spread of multid ...

Worldwide, tuberculosis (TB) is the leading cause of death due to a single infectious agent, claiming 1.6 million human lives and causing >10 million new cases in 2017 alone, mostly in low-income regions. The intracellular pathogen Mycobacterium tuberculos ...

The development of antibiotic-resistant bacteria is a worldwide health-related emergency that calls for new tools to study the bacterial metabolism and to obtain fast diagnoses. Indeed, the conventional analysis time scale is too long and affects our abili ...

The major facilitator superfamily transporter Rv1410 and the lipoprotein LprG (Rv1411) are encoded by a conserved two-gene operon and contribute to virulence in Mycobacterium tuberculosis. Rv1410 was originally postulated to function as a drug efflux pump, ...

Cell division is one of the most primordial cellular processes and is essential for life propagation. It is composed of crucial events, namely genome duplication, chromosomes segregation and membrane separation. Failure of these processes will have dramati ...

A multitarget approach to drug discovery inhibiting Mycobacterium tuberculosis PyrG and PanK

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Single-cell analysis of the interactions between Mycobacterium tuberculosis and macrophages

Investigating the composition and recruitment of the mycobacterial ImuA'-ImuB-DnaE2 mutasome

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers

Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages

Generating macrocyclic inhibitors of protein-protein interactions

NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism

Coordination between cell growth, division and chromosome replication cycles in mycobacteria

FasR Regulates Fatty Acid Biosynthesis and Is Essential for Virulence of Mycobacterium tuberculosis

Synthesis and Structure-Activity Relationship Studies of C2-Modified Analogs of the Antimycobacterial Natural Product Pyridomycin

Polarly Localized EccE(1) Is Required for ESX-1 Function and Stabilization of ESX-1 Membrane Proteins in Mycobacterium tuberculosis

High resolution CryoEM structure of the ring-shaped virulence factor EspB from Mycobacterium tuberculosis

New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosis

Time-lapse high-resolution microscopy to study the morphogenesis of microorganisms

Macrocycle synthesis strategy based on step-wise “adding and reacting” three components enables screening of large combinatorial libraries

Preexisting variation in DNA damage response predicts the fate of single mycobacteria under stress

Monitoring Tuberculosis Drug Activity in Live Animals by Using Near-Infrared Fluorescence Imaging

Innovative Tools and in vivo Methods for Tuberculosis Drug Discovery and Development

A Rapid Unraveling of the Activity and Antibiotic Susceptibility of Mycobacteria

Increased drug permeability of a stiffened mycobacterial outer membrane in cells lacking MFS transporter Rv1410 and lipoprotein LprG

Single-cell studies of Mycobacterium smegmatis cell cycle using time-lapse fluorescence microscopy