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John McKinney

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Related publications (73)

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Contrasting persistence strategies in Salmonella and Mycobacterium

John McKinney, Anna De Graff Tischler

Long-term survival of persistent bacterial pathogens in mammalian hosts critically depends on their ability to avoid elimination by innate and adaptive immune responses. The persistent human pathogens that cause typhoid fever and tuberculosis exemplify alt ...

2010

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

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

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

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

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

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

Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis

Jeffrey Alan Hubbell, Melody Swartz, John McKinney, Neeraj Dhar, Alexandre de Titta, Marie Ballester, Cyntia De Piano

Vaccines that drive robust T-cell immunity against Mycobacterium tuberculosis (Mtb) are needed both for prophylactic and therapeutic purposes. We have recently developed a synthetic vaccine delivery platform with Pluronic-stabilized polypropylene sulfide n ...

2011

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

John McKinney, 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

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

Georg Fantner, John McKinney, 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

Quantitative Mass Spectrometry Reveals Plasticity of Metabolic Networks in Mycobacterium smegmatis

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

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

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

Dielectrophoresis-based purification of antibiotic-treated bacterial subpopulations

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

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

Dielectrophoresis as a single cell characterization method for bacteria

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

Seeing and Touching the Mycomembrane at the Nanoscale

John McKinney, Georg Fantner

Mycobacteria have unique cell envelopes, surface properties and growth dynamics, which all play a part in the ability of these important pathogens to infect, evade host immunity, disseminate and to resist antibiotic challenges. Recent atomic force microsco ...

American Society for Microbiology2021

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

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

John McKinney, Neeraj Dhar, Muhittin Emre Özdemir

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

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

Expression of the leptin receptor outside of bone marrow-derived cells regulates tuberculosis control and lung macrophage MHC expression

John McKinney

Leptin is a pleiotropic hormone proposed to link nutritional status to the development of strong Th1 immunity. Because Mycobacterium tuberculosis control is affected by starvation and diabetes, we studied the role of the leptin receptor in regulating disti ...

American Association of Immunologists ; Oxford University Press2011

Revealing Antibiotic Tolerance of the Mycobacterium smegmatis Xanthine/Uracil Permease Mutant Using Microfluidics and Single-Cell Analysis

John McKinney, Neeraj Dhar, Meltem Elitas

To reveal rare phenotypes in bacterial populations, conventional microbiology tools should be advanced to generate rapid, quantitative, accurate, and high-throughput data. The main drawbacks of widely used traditional methods for antibiotic studies include ...

MDPI2021

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

John McKinney, Neeraj Dhar, 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

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

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

John McKinney, Chiara Toniolo, Matthieu Jean-Hubert Delincé

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

Structural Basis for Benzothiazinone-Mediated Killing of Mycobacterium tuberculosis

Paul Joseph Dyson, Stewart Cole, John McKinney, Florence Pojer, Neeraj Dhar, Joao Pedro De Almeida Neres

The benzothiazinone BTZ043 is a tuberculosis drug candidate with nanomolar whole-cell activity. BTZ043 targets the DprE1 catalytic component of the essential enzyme decaprenylphosphoryl-beta-D-ribofuranose-2'-epimerase, thus blocking biosynthesis of arabin ...

American Association for the Advancement of Science2012