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

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The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. ...

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Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment

Jacques Fellay, Christian Axel Wandall Thorball, Alessandro Borghesi

Background: The primary hurdle for the eradication of HIV-1 is the establishment of a latent viral reservoir early after primary infection. Here, we investigated the potential influence of human genetic variation on the HIV-1 reservoir size and its decay r ...

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Genomic Characterization of Mycobacterium lepraeto Explore Transmission Patterns Identifies New Subtype in Bangladesh

Stewart Cole, Andrej Benjak, Charlotte Avanzi

Mycobacterium leprae, the causative agent of leprosy, is an unculturable bacterium with a considerably reduced genome (3.27 Mb) compared to homologues mycobacteria from the same ancestry. In 2001, the genome ofM. lepraewas first described and subsequently ...

Frontiers Media SA2020

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

Stewart Cole, Raphael Christopher Sommer

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 ...

AMER SOC MICROBIOLOGY2019

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

Raphael Christopher Sommer

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 ...

EPFL2019

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

John McKinney, Neeraj Dhar, Giulia Manina, Lalit Kumar Singh

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 ...

2019

A Rapid Unraveling of the Activity and Antibiotic Susceptibility of Mycobacteria

Giovanni Dietler, Sandor Kasas, Giovanni Longo, Leonardo Venturelli

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 ...

AMER SOC MICROBIOLOGY2019

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Joëlle Xiao Yuan Ven

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 ...

EPFL2019

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

Thierry Buclin, Stewart Cole, Jeff Pitteloud, Anthony Vocat

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 ...

2019

HIV peptidome-wide association study reveals patient-specific epitope repertoires associated with HIV control

Jacques Fellay, Paul Jack Mc Laren, Nimisha Chaturvedi

Genetic variation in the peptide-binding groove of the highly polymorphic HLA class I molecules has repeatedly been associated with HIV-1 control and progression to AIDS, accounting for up to 12% of the variation in HIV-1 set point viral load (spVL). This ...

National Academy of Sciences2019

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

Georg Fantner, Haig Alexander Eskandarian

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, ...

2019

Synthesis, biology, computational studies and in vitro controlled release of new isoniazid-based adamantane derivatives

Stewart Cole, Anthony Vocat

Aim: There is a necessity for new drugs to be more efficient than today's standard due to the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) Results/methodology: 12 new isoniazid-based adamantane derivatives were synthesized and te ...

FUTURE SCI LTD2019