New tuberculosis drugs on the horizon

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Ribonucleotide reductase (RNR) is an essential enzyme in DNA biogenesis and a target of several chemotherapeutics. Here, we investigate how antileukemic drugs (e.g., clofarabine [CIF]) that target one of the two subunits of RNR, RNR-alpha, affect noncanoni ...

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 ...

Living organisms can catalyze many thousands of biochemical reactions that they use to convert energy and matter, which provides them with the essentials for life. The sum of these chemical reactions happening in an organism is called metabo-lism. Understa ...

A case of Mycobacterium leprae rifampin resistance after irregular antile- prosy treatments since 1971 is reported. Whole-genome sequencing from four longi- tudinal samples indicated relapse due to acquired rifampin resistance and not to re- infection with ...

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 ...

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 ...

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 ...

Stereotyped as a nexus of dNTP synthesis, the dual-subunit enzyme - ribonucleotide reductase (RNR) - is coming into view as a paradigm of oligomerization and moonlighting behavior. In the present issue of `omics', we discuss what makes the larger subunit o ...

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 ...

The emergence of Mycobacterium tuberculosis strains resistant to current first-line antibiotic regimens constitutes a major global health threat. New treatments against multidrug-resistant tuberculosis (MDR-TB) are thus eagerly needed in particular in coun ...

The peptidoglycan (PG) sacculus provides bacteria with the mechanical strength to maintain cell shape and resist osmotic stress. Enlargement of the mesh-like sacculus requires the combined activity of peptidoglycan synthases and hydrolases. In Escherichia ...

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 ...

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 ...

The sum of all of the interactions between single bacteria and host cells determines if an infection is cleared, controlled, or progresses at the whole host-organism level. These individual interactions have independent trajectories defined by diverse and ...

New tuberculosis drugs on the horizon

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Clofarabine Commandeers the RNR-alpha-ZRANB3 Nuclear Signaling Axis

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

Modeling, predicting and mining metabolism at atom-level resolution

Emergence of Mycobacterium leprae Rifampin Resistance Evaluated by Whole-Genome Sequencing after 48 Years of Irregular Treatment

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

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

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

The more the merrier: how homo-oligomerization alters the interactome and function of ribonucleotide reductase

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

Development and validation of a multiplex UHPLC-MS/MS method for the determination of the investigational antibiotic against multi-resistant tuberculosis macozinone (PBTZ169) and five active metabolites in human plasma

Outer membrane lipoprotein NlpI scaffolds peptidoglycan hydrolases within multi-enzyme complexes in Escherichia coli

A Rapid Unraveling of the Activity and Antibiotic Susceptibility of Mycobacteria

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

Do chance encounters between heterogeneous cells shape the outcome of tuberculosis infections?