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John McKinney

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Publications associées (74)

Computational Analysis of the Mutual Constraints between Single‐Cell Growth and Division Control Models

John McKinney, Neeraj Dhar, Ambroise Roger Vuaridel, Gaëlle Madeleine Vuaridel

Three models of division control are proposed to achieve cell size homeostasis: sizer, timer, and adder. However, few published studies of division control take into account the dynamics of single‐cell growth and most assume that single‐cell growth is expo ...

2019

Elucidating the role of (p)ppGpp in mycobacterial persistence against antibiotics

Cyntia De Piano, John McKinney, Neeraj Dhar, Ekaterina Gelman, Ashima Bhaskar

2018

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

John McKinney, Georg Fantner, 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

Photothermal Off-Resonance Tapping for Rapid and Gentle Atomic Force Imaging of Live Cells

John McKinney, Georg Fantner, Adrian Pascal Nievergelt, Haig Alexander Eskandarian, Charlène Cécile Geneviève Brillard

Imaging living cells by atomic force microscopy (AFM) promises not only high-resolution topographical data, but additionally, mechanical contrast, both of which are not obtainable with other microscopy techniques. Such imaging is however challenging, as ce ...

2018

Fluorescent Benzothiazinone Analogues Efficiently and Selectively Label Dpre1 in Mycobacteria and Actinobacteria

Paul Joseph Dyson, Thierry Laroche, John McKinney, Stewart Cole, Neeraj Dhar, Raphael Christopher Sommer, Joao Pedro De Almeida Neres, Raju Mukherjee, Jérémie Piton

Benzothiazinones (BTZ) are highly potent bactericidal inhibitors of mycobacteria and the lead compound, BTZ043, and the optimized drug candidate, PBTZ169, have potential for the treatment of tuberculosis. Here, we exploited the tractability of the BTZ scaf ...

2018

A microfluidic cell-trapping device to study dynamic host-microbe interactions at the single-cell level

Matthieu Jean-Hubert Delincé, John McKinney, Chiara Toniolo

Single-cell imaging of host-microbe interactions over time is impeded by cellular motility because the cells under scrutiny tend to migrate out of the imaging field. To overcome this technical challenge, we developed a microfluidic platform for imaging hun ...

ELSEVIER ACADEMIC PRESS INC2018

Dielectrophoresis as a single cell characterization method for bacteria

Philippe Renaud, Thomas Michael Braschler, John McKinney, Neeraj Dhar, Ana Valero

Real-time, quantitative characterization of cells at single-cell resolution, particularly while maintain- ing their intrinsic properties and without affecting cellular processes, is of primary importance in modern biological assays. Dielectrophoresis is a ...

Iop Publishing Ltd2017

Division site selection linked to inherited cell surface wave troughs in mycobacteria

Joëlle Xiao Yuan Ven, John McKinney, Neeraj Dhar, Georg Fantner, Pascal Damian Odermatt, Adrian Pascal Nievergelt, Mélanie Thérèse Marie Hannebelle, Haig Alexander Eskandarian

Cell division is tightly controlled in space and time to maintain cell size and ploidy within narrow bounds. In bacteria, the canonical Minicell (Min) and nucleoid occlusion (Noc) systems together ensure that division is restricted to midcell after complet ...

2017

Identification of aminopyrimidine-sulfonamides as potent modulators of Wag31-mediated cell elongation in mycobacteria

Kai Johnsson, Gaëlle Séraphine Kolly, Graham Knott, John McKinney, Stewart Cole, Neeraj Dhar, Monica Rengifo Gonzalez, Ruben Hartkoorn, Isabella Santi, Edina Rita Székely, François Signorino-Gelo, Jan Lars Rybniker, Anthony Vocat

There is an urgent need to discover new antitubercular agents with novel mechanisms of action in order to tackle the scourge of drug-resistant tuberculosis. Here, we report the identification of such a molecule - an AminoPYrimidine-Sulfonamide (APYS1) that ...

Wiley-Blackwell2017

The Inosine Monophosphate Dehydrogenase, GuaB2, Is a Vulnerable New Bactericidal Drug Target for Tuberculosis

John McKinney, Stewart Cole, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn, Raphael Christopher Sommer, Anthony Vocat, Andréanne Lupien

VCC234718, a molecule with growth inhibitory activity against Mycobacterium tuberculosis (Mtb), was identified by phenotypic screening of a 15344-compound library. Sequencing of a VCC234718-resistant mutant identified a Y487C substitution in the inosine mo ...

Amer Chemical Soc2017

The studies of ParA and ParB dynamics reveal asymmetry of chromosome segregation in mycobacteria

John McKinney, Djenet Bousbaine, Isabella Santi

Active segregation of bacterial chromosomes usually involves the action of ParB proteins, which bind in proximity of chromosomal origin (oriC) regions forming nucleoprotein complexes - segrosomes. Newly duplicated segrosomes are moved either uni- or bidire ...

Wiley2017

Phenotypic Heterogeneity in Mycobacterium tuberculosis

John McKinney, Neeraj Dhar, Giulia Manina

The interaction between the host and the pathogen is extremely complex and is affected by anatomical, physiological, and immunological diversity in the microenvironments, leading to phenotypic diversity of the pathogen. Phenotypic heterogeneity, defined as ...

Amer Soc Microbiology2016

A rheostat mechanism governs the bifurcation of carbon flux in mycobacteria

John McKinney, Florence Pojer, Matteo Dal Peraro, Tarun Chopra, Paul Murima, Giulia Fonti

Fatty acid metabolism is an important feature of the pathogenicity of Mycobacterium tuberculosis during infection. Consumption of fatty acids requires regulation of carbon flux bifurcation between the oxidative TCA cycle and the glyoxylate shunt. In Escher ...

Nature Publishing Group2016

Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor

John McKinney, Neeraj Dhar, François Signorino-Gelo

Despite being one of the first antitubercular agents identified, isoniazid (INH) is still the most prescribed drug for prophylaxis and tuberculosis (TB) treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of ison ...

Elsevier Science Bv2016

Mycobacterium tuberculosis Resists Stress by Regulating PE19 Expression

John McKinney, Anna De Graff Tischler

Mycobacterium tuberculosis requires the phosphate-sensing signal transduction system Pst/SenX3-RegX3 to resist host immune responses. A Delta pstA1 mutant lacking a Pst phosphate uptake system component is hypersensitive to diverse stress conditions in vit ...

American Society for Microbiology2016

A microfluidic cell-trapping device for single-cell tracking of host-microbe interactions

Matthieu Jean-Hubert Delincé, John McKinney, Jean-Baptiste Bureau, Thierry Soldati

The impact of cellular individuality on host-microbe interactions is increasingly appreciated but studying the temporal dynamics of single-cell behavior in this context remains technically challenging. Here we present a microfluidic platform, InfectChip, t ...

Royal Society of Chemistry2016

Mycobacterium tuberculosis Phosphate Uptake System Component PstA2 Is Not Required for Gene Regulation or Virulence

John McKinney, Anna De Graff Tischler

The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane-spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for r ...

Public Library of Science2016

Stressed Mycobacteria Use the Chaperone ClpB to Sequester Irreversibly Oxidized Proteins Asymmetrically Within and Between Cells

Michaël Unser, Olivia Mariani, John McKinney, Neeraj Dhar

Mycobacterium tuberculosis (Mtb) defends itself against host immunity and chemotherapy at several levels, including the repair or degradation of irreversibly oxidized proteins (IOPs). To investigate how Mtb deals with IOPs that can neither be repaired nor ...

Cell Press2015

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

Single-Cell Tracking Reveals Antibiotic-Induced Changes in Mycobacterial Energy Metabolism

John McKinney, Muhittin Emre Özdemir, Zeljka Maglica

ATP is a key molecule of cell physiology, but despite its importance, there are currently no methods for monitoring single-cell ATP fluctuations in live bacteria. This is a major obstacle in studies of bacterial energy metabolism, because there is a growin ...

American Society for Microbiology2015

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