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Concept

Vaccin bilié de Calmette et Guérin

Publications associées (21)

Optimal control of the spatial allocation of COVID-19 vaccines: Italy as a case study

Andrea Rinaldo, Enrico Bertuzzo, Lorenzo Mari, Damiano Pasetto, Joseph Chadi Benoit Lemaitre

While campaigns of vaccination against SARS-CoV-2 are underway across the world, communities face the challenge of a fair and effective distribution of a limited supply of doses. Current vaccine allocation strategies are based on criteria such as age or ri ...

2022

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

John McKinney, Neeraj Dhar, Giulia Manina

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

Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses

Jeffrey Alan Hubbell, Melody Swartz, Sachiko Hirosue, Alexandre de Titta

Background: Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of a ...

2017

Nitroarenes as Antitubercular Agents: Stereoelectronic Modulation to Mitigate Mutagenicity

Joao Pedro De Almeida Neres

Nitroarenes are less preferred in drug discovery due to their potential to be mutagenic. However, several nitroarenes were shown to be promising antitubercular agents with specific modes of action, namely, nitroimidazoles and benzothiazinones. The nitro gr ...

Wiley-V C H Verlag Gmbh2016

Host and pathogen genomics of severe pediatric infections

Samira Asgari

Infectious diseases are among the leading causes of human morbidity and mortality, with the greatest burden felt in the pediatric population. For any infectious disease, only a fraction of the exposed individuals develop clinical symptoms. These inter-indi ...

EPFL2016

2-Carboxyquinoxalines Kill Mycobacterium tuberculosis through Noncovalent Inhibition of DprE1

Stewart Cole, Neeraj Dhar, Florence Pojer, Ruben Hartkoorn, Gaëlle Séraphine Kolly, Joao Pedro De Almeida Neres

Phenotypic screening of a quinoxaline library against replicating Mycobacterium tuberculosis led to the identification of lead compound Ty38c (3-((4-methoxybenzyl)amino)-6-(trifluoromethyl)quinoxaline-2-carboxylic acid). With an MIC99 and MBC of 3.1 mu M, ...

American Chemical Society2015

Whole Cell Target Engagement Identifies Novel Inhibitors of Mycobacterium tuberculosis Decaprenylphosphoryl-beta-D-ribose Oxidase

John McKinney, Neeraj Dhar

We have targeted the Mycobacterium tuberculosis decaprenylphosphoryl-beta-D-ribose oxidase (Mt-DprE1) for potential chemotherapeutic intervention of tuberculosis. A multicopy suppression strategy that overexpressed Mt-DprEl in M. bovis BCG was used to prof ...

Amer Chemical Soc2015

Assessing essentiality of transketolase in Mycobacterium tuberculosis using an inducible protein degradation system

Stewart Cole, Claudia Sala, Anthony Vocat, Gaëlle Séraphine Kolly

Improved genetic tools are required to identify new drug targets in Mycobacterium tuberculosis. To this aim, genetic approaches, targeting either transcription and/or protein degradation, have been developed to appraise gene essentiality and to test the im ...

Wiley-Blackwell2014

In Vitro and In Vivo Activities of Three Oxazolidinones against Nonreplicating Mycobacterium tuberculosis

Stewart Cole, Neeraj Dhar, Claudia Sala, Anthony Vocat, Ming Zhang

Oxazolidinones represent a new class of antituberculosis drugs that exert their function by inhibiting protein synthesis. Here, we compared the activities of three oxazolidinones, linezolid, PNU-100480, and AZD5847, against latent tuberculosis using a simp ...

Amer Soc Microbiology2014

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

Stewart Cole, Swapna Uplekar

In mycobacteria, CycA a D-serine, L-and D-alanine, and glycine transporter also functions in the uptake of D-cycloserine, an important second-line anti-tubercular drug. A single nucleotide polymorphism identified in the cycA gene of BCG was hypothesized to ...

Public Library of Science2012

Genomics and transcriptomics of the Mycobacterium tuberculosis complex

Swapna Uplekar

The goal of eliminating tuberculosis (TB) by 2050 depends on the development of improved TB diagnostics, drugs and vaccines. Advances in these areas require a deep understanding of the disease and its causative agent, Mycobacterium tuberculosis (M. tb). My ...

EPFL2012

Effect of serial subculturing on the genetic composition and cytotoxic activity of Mycobacterium tuberculosis

Stewart Cole

Continuous subculture has been observed to produce changes in the virulence of micro-organisms, e.g. rabies virus, poliovirus and Mycobacterium bovis BCG. The latter has been used as a vaccine for tuberculosis for the last 100 years; however, in some insta ...

2010

A Simple Model for Testing Drugs against Non-replicating Mycobacterium tuberculosis

Stewart Cole, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn, Ming Zhang

Non-replicating or dormant cells of Mycobacterium tuberculosis constitute a challenge to tuberculosis (TB) therapy because of their tolerance or phenotypic resistance to most drugs. Here, we propose a simple model for testing drugs against non-growing cell ...

2010

Mycobacterium leprae: genes, pseudogenes and genetic diversity

Stewart Cole, Pushpendra Singh

Leprosy, which has afflicted human populations for millenia, results from infection with Mycobacterium leprae, an unculturable pathogen with an exceptionally long generation time. Considerable insight into the biology and drug resistance of the leprosy bac ...

2010

A comprehensive survey of single nucleotide polymorphisms (SNPs) across Mycobacterium bovis strains and M. bovis BCG vaccine strains refines the genealogy and defines a minimal set of SNPs that separate virulent M. bovis strains and M. bovis BCG strains

Stewart Cole, Swapna Uplekar

To further unravel the mechanisms responsible for attenuation of the tuberculosis vaccine Mycobacterium bovis BCG, comparative genomics was used to identify single nucleotide polymorphisms (SNPs) that differed between sequenced strains of Mycobacterium bov ...

2009

Boosting with a DNA vaccine expressing ESAT-6 (DNAE6) obliterates the protection imparted by recombinant BCG (rBCGE6) against aerosol Mycobacterium tuberculosis infection in guinea pigs

Neeraj Dhar

Owing to its highly immunodominant nature and ability to induce long-lived memory immunity, ESAT-6. a prominent antigen of Mycobacterium tuberculosis, has been employed in several approaches to develop tuberculosis vaccines Here, for the first time, we com ...

2009

Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP

Stewart Cole

Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach to identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two of the most widely used attenuated strains in the ...

2008

A novel drug discovery concept for tuberculosis: inhibition of bacterial and host cell signalling

Stewart Cole, Edina Rita Székely

The Mycobacterium tuberculosis genome encodes for eleven eukaryotic-like Ser/Thr protein kinases. At least three of these (PknA, PknB and PknG) are essential for bacterial growth and survival. PknG is secreted by pathogenic mycobacteria, in macrophages to ...

2008

Genome plasticity of BCG and impact on vaccine efficacy

Stewart Cole

To understand the evolution, attenuation, and variable protective efficacy of bacillus Calmette-Guérin (BCG) vaccines, Mycobacterium bovis BCG Pasteur 1173P2 has been subjected to comparative genome and transcriptome analysis. The 4,374,522-bp genome conta ...

National Academy of Sciences2007