Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA-independent virulence

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Functional characterization of the virulence determinant ESX-1 from Mycobacterium tuberculosis

Paloma Julia Soler Arnedo

Tuberculosis (TB) is a chronic infectious disease that mainly affects the lungs and causes extensive human morbidity and mortality. It results from infection with Mycobacterium tuberculosis, a slow-growing intracellular pathogen that can replicate and surv ...

EPFL2018

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

Stewart Cole

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 ...

Nature Research2018

EspL is essential for virulence and stabilizes EspE, EspF and EspH levels in Mycobacterium tuberculosis

Sofia Ulrika Magnusdotter Von Schultz, Stewart Cole, Claudia Sala, Andrej Benjak, Nina Theres Odermatt, Paloma Julia Soler Arnedo

The ESX-1, type VII, secretion system represents the major virulence determinant of Mycobacterium tuberculosis, one of the most successful intracellular pathogens. Here, by combining genetic and high-throughput approaches, we show that EspL, a protein of 1 ...

PUBLIC LIBRARY SCIENCE2018

Arylvinylpiperazine Amides, a New Class of Potent Inhibitors Targeting QcrB of Mycobacterium tuberculosis

Stewart Cole, Andrej Benjak, Anthony Vocat, Jérémie Piton, Raphael Christopher Sommer, Shi-Yan Caroline Foo, Andréanne Lupien

New drugs are needed to control the current tuberculosis (TB) pandemic caused by infection with Mycobacterium tuberculosis. We report here on our work with AX-35, an arylvinylpiperazine amide, and four related analogs, which are potent antitubercular agent ...

AMER SOC MICROBIOLOGY2018

Deciphering the molecular basis of mycobacteria and lipoglycan recognition by the C-type lectin Dectin-2

Alexiane Clara Decout

Dectin-2 is a C-type lectin involved in the recognition of several pathogens such as Aspergillus fumigatus, Candida albicans, Schistosoma mansonii, and Mycobacterium tuberculosis that triggers Th17 immune responses. Identifying pathogen ligands and underst ...

Nature Research2018

Structure-Based Drug Design and Characterization of Sulfonyl-Piperazine Benzothiazinone Inhibitors of DprE1 from Mycobacterium tuberculosis

Stewart Cole, Anthony Vocat, Jérémie Piton, Shi-Yan Caroline Foo, Andréanne Lupien

Macozinone (MCZ) is a tuberculosis (TB) drug candidate that specifically targets the essential flavoenzyme DprE1, thereby blocking synthesis of the cell wall precursor decaprenyl phosphoarabinose (DPA) and provoking lysis of Mycobacterium tuberculosis. As ...

AMER SOC MICROBIOLOGY2018

Genetics of human susceptibility to active and latent tuberculosis: present knowledge and future perspectives

Jacques Fellay, Nimisha Chaturvedi

Tuberculosis is an ancient human disease, estimated to have originated and evolved over thousands of years alongside modern human populations. Despite considerable advances in disease control, tuberculosis remains one of the world's deadliest communicable ...

2018

Maturing Mycobacterium smegmatis peptidoglycan requires non-canonical crosslinks to maintain shape

Georg Fantner, John McKinney, Haig Alexander Eskandarian

In most well-studied rod-shaped bacteria, peptidoglycan is primarily crosslinked by penicillin-binding proteins (PBPs). However, in mycobacteria, crosslinks formed by L,D-transpeptidases (LDTs) are highly abundant. To elucidate the role of these unusual cr ...

ELIFE SCIENCES PUBLICATIONS LTD2018

More Medicines for Tuberculosis: Fuelling Drug Discovery against Mycobacterium tuberculosis

Shi-Yan Caroline Foo

Tuberculosis (TB), whose etiological agent is Mycobacterium tuberculosis (M. tuberculosis), has plagued humanity since antiquity. Even with chemotherapy available today, TB is the leading cause of death due to an infectious disease. Modern day factors, suc ...

EPFL2018

Optimized Background Regimen for Treatment of Active Tuberculosis with the Next-Generation Benzothiazinone Macozinone (PBTZ169)

Stewart Cole, Anthony Vocat, Shi-Yan Caroline Foo, Andréanne Lupien

The efficacy of the standardized four-drug regimen (comprising isoniazid, rifampin, pyrazinamide, and ethambutol) for the treatment of tuberculosis (TB) is menaced by the emergence of multidrug-resistant (MDR) and extensively drugresistant (XDR) strains of ...

AMER SOC MICROBIOLOGY2018