A Point Mutation in cycA Partially Contributes to the D-cycloserine Resistance Trait of Mycobacterium bovis BCG Vaccine Strains

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

Stewart Cole, Claudia Sala, Ming Zhang, Jérémie Piton, Paloma Julia Soler Arnedo

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 ...

American Society for Microbiology2020

Somatic Mitochondrial DNA Point Mutations Used as Biomarkers to Demonstrate Genomic Heterogeneity in Primary Prostate Cancer

Paul Refinetti, Per Olaf Ekstrom

Primary prostate tumor heterogeneity is poorly understood, leaving research efforts with challenges regarding the initiation and advancement of the disease. The growth of tumor cells is accompanied by mutations in nuclear and in mitochondrial genomes. Thus ...

HINDAWI LTD2020

Direct coupling analysis of epistasis in allosteric materials

Matthieu Wyart, Riccardo Ravasio, Carolina Brito Carvalho dos Santos, Barbara Bravi

In allosteric proteins, the binding of a ligand modifies function at a distant active site. Such allosteric pathways can be used as target for drug design, generating considerable interest in inferring them from sequence alignment data. Currently, differen ...

2020

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

Stewart Cole, Florence Pojer, Jérémie Piton

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 ...

2020

Endoplasmic Reticulum and Lysosomal Quality Control of Four Nonsense Mutants of Iduronate 2-Sulfatase Linked to Hunter's Syndrome

Maurizio Molinari, Andrea Cavalli

Hunter's syndrome (mucopolysaccharidosis type II) is a rare X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. Motivated by the case of a child affected by this syndrome, we compared the intracellular fate of w ...

2020

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

Stewart Cole, Andrej Benjak, Charlotte Avanzi, Philippe Busso

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 ...

AMER SOC MICROBIOLOGY2020

Population Genomics of Mycobacterium leprae Reveals a New Genotype in Madagascar and the Comoros

Stewart Cole, Stefanie Boy-Röttger, Andrej Benjak, Charlotte Avanzi, Philippe Busso, Pushpendra Singh, Thyago Leal Calvo

Human settlement of Madagascar traces back to the beginning of the first millennium with the arrival of Austronesians from Southeast Asia, followed by migrations from Africa and the Middle East. Remains of these different cultural, genetic, and linguistic ...

Frontiers Media SA2020

Advanced Quantification Methods To Improve the 18b Dormancy Model for Assessing the Activity of Tuberculosis Drugs In Vitro

Stewart Cole, Claudia Sala

One of the reasons for the lengthy tuberculosis (TB) treatment is the difficulty to treat the nonmultiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models ...

AMER SOC MICROBIOLOGY2020

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

Mélanie Thérèse Marie Hannebelle

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 ...

EPFL2020

Trametinib Induces the Stabilization of a Dual GNAQ p.Gly48Leu-and FGFR4 p.Cys172Gly-Mutated Uveal Melanoma. The Role of Molecular Modelling in Personalized Oncology

Olivier Michielin, Krisztian Homicsko, Alexandre Wicky

We report a case of an uveal melanoma patient with GNAQ p.Gly48Leu who responded to MEK inhibition. At the time of the molecular analysis, the pathogenicity of the mutation was unknown. A tridimensional structural analysis showed that G alpha(q) can adopt ...

2020

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