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Neeraj Dhar

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Related publications (53)

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Dynamic Persistence of Antibiotic-Stressed Mycobacteria

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

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

Mycobacterium tuberculosis persistence mutants identified by screening in isoniazid-treated mice

John McKinney, Neeraj Dhar

Tuberculosis (TB) is notoriously difficult to cure, requiring administration of multiple antibiotics for 6 mo or longer. Conventional anti-TB drugs inhibit biosynthetic processes involved in cell growth and division, such as DNA replication, RNA transcript ...

2010

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

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

Dynamic persistence of UPEC intracellular bacterial communities in a human bladder-chip model of urinary tract infection

Graham Knott, John McKinney, Neeraj Dhar, Vivek Vijay Thacker, François Signorino-Gelo, Kunal Sharma, Thomas Marie Simonet

Uropathogenic Escherichia coli (UPEC) proliferate within superficial bladder umbrella cells to form intracellular bacterial communities (IBCs) during early stages of urinary tract infections. However, the dynamic responses of IBCs to host stresses and anti ...

2021

Uptake-independent killing of macrophages by extracellular Mycobacterium tuberculosis aggregates

John McKinney, Neeraj Dhar, Chiara Toniolo

Mycobacterium tuberculosis (Mtb) infection is initiated by inhalation of bacteria into lung alveoli, where they are phagocytosed by resident macrophages. Intracellular Mtb replication induces the death of the infected macrophages and the release of bacteri ...

WILEY2023

Streptomycin-Starved Mycobacterium tuberculosis 18b, a Drug Discovery Tool for Latent Tuberculosis

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

Mycobacterium tuberculosis 18b, a streptomycin (STR)-dependent mutant that enters a viable but nonreplicating state in the absence of STR, has been developed as a simple model for drug testing against dormant bacilli. Here, we further evaluated the STR-sta ...

Amer Soc Microbiology2012

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

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

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

Bioluminescence for Assessing Drug Potency against Nonreplicating Mycobacterium tuberculosis

Stewart Cole, Neeraj Dhar, Claudia Sala, Anthony Vocat, Ruben Hartkoorn, Ming Zhang, Benoit Lechartier

Targeting dormant Mycobacterium tuberculosis represents a challenge to antituberculosis drug discovery programs. We previously reported and validated the use of the streptomycin (STR)-dependent M. tuberculosis 18b strain as a tool for assessing drug potenc ...

American Society for Microbiology2015

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

Amidation of glutamate residues in mycobacterial peptidoglycan is essential for cell wall cross-linking

Neeraj Dhar

IntroductionMycobacteria assemble a complex cell wall with cross-linked peptidoglycan (PG) which plays an essential role in maintenance of cell wall integrity and tolerance to osmotic pressure. We previously demonstrated that various hydrolytic enzymes are ...

FRONTIERS MEDIA SA2023

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

The Phosphatidyl-myo-Inositol Mannosyltransferase PimA Is Essential for Mycobacterium tuberculosis Growth In Vitro and In Vivo

Stewart Cole, Neeraj Dhar, Claudia Sala, Ming Zhang, Gaëlle Séraphine Kolly

The cell envelope of Mycobacterium tuberculosis contains glycans and lipids of peculiar structure that play prominent roles in the biology and pathogenesis of tuberculosis. Consequently, the chemical structure and biosynthesis of the cell wall have been in ...

American Society for Microbiology2014