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John McKinney

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Publications associées (74)

Rapid Cytolysis of Mycobacterium tuberculosis by Faropenem, an Orally Bioavailable beta-Lactam Antibiotic

John McKinney, Neeraj Dhar, François Signorino-Gelo

Recent clinical studies indicate that meropenem, a beta-lactam antibiotic, is a promising candidate for therapy of drug-resistant tuberculosis. However, meropenem is chemically unstable, requires frequent intravenous injection, and must be combined with a ...

American Society for Microbiology2015

Stress and Host Immunity Amplify Mycobacterium tuberculosis Phenotypic Heterogeneity and Induce Nongrowing Metabolically Active Forms

John McKinney, Neeraj Dhar, Giulia Manina

Nonreplicating and metabolically quiescent bacteria are implicated in latent tuberculosis infections and relapses following "sterilizing" chemotherapy. However, evidence linking bacterial dormancy and persistence in vivo is largely inconclusive. Here we me ...

Cell Press2015

Combinations of beta-Lactam Antibiotics Currently in Clinical Trials Are Efficacious in a DHP-I-Deficient Mouse Model of Tuberculosis Infection

John McKinney, Neeraj Dhar

We report here a dehydropeptidase-deficient murine model of tuberculosis (TB) infection that is able to partially uncover the efficacy of marketed broad-spectrum beta-lactam antibiotics alone and in combination. Reductions of up to 2 log CFU in the lungs o ...

American Society for Microbiology2015

Chromosome Organization and Replisome Dynamics in Mycobacterium smegmatis

John McKinney, Isabella Santi

Subcellular organization of the bacterial nucleoid and spatiotemporal dynamics of DNA replication and segregation have been studied intensively, but the functional link between these processes remains poorly understood. Here we use quantitative time-lapse ...

American Society for Microbiology2015

Assessing the essentiality of the decaprenyl-phospho-D-arabinofuranose pathway in Mycobacterium tuberculosis using conditional mutants

Gaëlle Séraphine Kolly, John McKinney, Stewart Cole, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn

In Mycobacterium tuberculosis the decaprenyl-phospho-d-arabinofuranose (DPA) pathway is a validated target for the drugs ethambutol and benzothiazinones. To identify other potential drug targets in the pathway, we generated conditional knock-down mutants o ...

Wiley-Blackwell2014

Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism

John McKinney, Neeraj Dhar, Muhittin Emre Özdemir, Ping Lu

Bedaquiline (BDQ), an ATP synthase inhibitor, is the first drug to be approved for treatment of multidrug-resistant tuberculosis in decades. Though BDQ has shown excellent efficacy in clinical trials, its early bactericidal activity during the first week o ...

Nature Publishing Group2014

4-Aminoquinolone Piperidine Amides: Noncovalent Inhibitors of DprE1 with Long Residence Time and Potent Antimycobacterial Activity

John McKinney, Neeraj Dhar, Joao Pedro De Almeida Neres, François Signorino-Gelo

4-Aminoquinolone piperidine amides (AQs) were identified as a novel scaffold starting from a whole cell screen, with potent cidality on Mycobacterium tuberculosis (Mtb). Evaluation of the minimum inhibitory concentrations, followed by whole genome sequenci ...

Amer Chemical Soc2014

Pathogenesis of Mycobacterium tuberculosis and its Interaction with the Host Organism Preface

John McKinney

Springer-Verlag2014

Establishment and Validation of Whole-Cell Based Fluorescence Assays to Identify Anti-Mycobacterial Compounds Using the Acanthamoeba castellanii - Mycobacterium marinum Host-Pathogen System

Hajer Ouertatani-Sakouhi, John McKinney, Thierry Soldati

Tuberculosis is considered to be one of the world's deadliest disease with 2 million deaths each year. The need for new antitubercular drugs is further exacerbated by the emergence of drug-resistance strains. Despite multiple recent efforts, the majority o ...

Public Library of Science2014

Targeting Bacterial Central Metabolism for Drug Development

John McKinney, Paul Murima

Current antibiotics, derived mainly from natural sources, inhibit a narrow spectrum of cellular processes, namely DNA replication, protein synthesis, and cell wall biosynthesis. With the worldwide explosion of drug resistance, there is renewed interest in ...

Elsevier2014

Dielectrophoresis-based purification of antibiotic-treated bacterial subpopulations

Philippe Renaud, John McKinney, Neeraj Dhar, Meltem Elitas, Rodrigo Martinez Duarte

Persistence of bacteria during antibiotic therapy is a widespread phenomenon, of particular importance in refractory mycobacterial infections such as leprosy and tuberculosis. Persistence is characterized by the phenotypic tolerance of a subpopulation of b ...

Royal Soc Chemistry2014

Quantitative Mass Spectrometry Reveals Plasticity of Metabolic Networks in Mycobacterium smegmatis

Marc Moniatte, Diego Chiappe, John McKinney, Tarun Chopra, Florence Armand, Romain Hamelin

Mycobacterium tuberculosis has a remarkable ability to persist within the human host as a clinically inapparent or chronically active infection. Fatty acids are thought to be an important carbon source used by the bacteria during long term infection. Catab ...

Amer Soc Biochemistry Molecular Biology Inc2014

A Single-Cell Perspective on Non-Growing but Metabolically Active (NGMA) Bacteria

John McKinney, Giulia Manina

A long-standing and fundamental problem in microbiology is the non-trivial discrimination between live and dead cells. The existence of physically intact and possibly viable bacterial cells that fail to replicate during a more or less protracted period of ...

Springer-Verlag2014

Single-cell dynamics of the chromosome replication and cell division cycles in mycobacteria

John McKinney, Neeraj Dhar, Djenet Bousbaine, Isabella Santi

During the bacterial cell cycle, chromosome replication and cell division must be coordinated with overall cell growth in order to maintain the correct ploidy and cell size. The spatial and temporal coordination of these processes in mycobacteria is not un ...

Nature Publishing Group2013

Dynamic Persistence of Antibiotic-Stressed Mycobacteria

John McKinney, Neeraj Dhar, Katrin Esther Schneider, François Signorino-Gelo

Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing "persisters." Using microflui ...

American Association for the Advancement of Science2013

A problem of persistence: still more questions than answers?

John McKinney

The current antibiotic resistance crisis has led to increased pressure to prioritize strategies to tackle the issue, with a strong focus being placed on the development of novel antimicrobials. However, one major obstacle that is often overlooked is persis ...

Nature Publishing Group2013

A vitamin B-12 transporter in Mycobacterium tuberculosis

John McKinney

Vitamin B-12-depende enzymes function in core biochemical pathways in Mycobacterium tuberculosis, an obligate pathogen whose metabolism in vivo is poorly understood. Although M. tuberculosis can access vitamin B-12 in vitro, it is uncertain whether the org ...

Royal Society, The2013

Mycobacterium tuberculosis Requires Phosphate-Responsive Gene Regulation To Resist Host Immunity

John McKinney, Anna De Graff Tischler

Mycobacterium tuberculosis persists in the tissues of mammalian hosts despite inducing a robust immune response dominated by the macrophage-activating cytokine gamma interferon (IFN-gamma). We identified the M. tuberculosis phosphate-specific transport (Ps ...

American Society for Microbiology2013

Cholesterol Catabolism by Mycobacterium tuberculosis Requires Transcriptional and Metabolic Adaptations

John McKinney

To understand the adaptation of Mycobacterium tuberculosis to the intracellular environment, we used comprehensive metabolite profiling to identify the biochemical pathways utilized during growth on cholesterol, a critical carbon source during chronic infe ...

2012

Malachite Green Interferes with Postantibiotic Recovery of Mycobacteria

John McKinney, Neeraj Dhar, Ekaterina Gelman

The genus Mycobacterium comprises slow-growing species with generation times ranging from hours to weeks. The protracted incubation time before colonies appear on solid culture medium can result in overgrowth by faster-growing microorganisms. To prevent co ...

2012

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