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Neeraj Dhar

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Publications associées (54)

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

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

Structural Basis for Benzothiazinone-Mediated Killing of Mycobacterium tuberculosis

Paul Joseph Dyson, John McKinney, Stewart Cole, Neeraj Dhar, Florence Pojer, Elizabeth Fullam, 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

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

Stewart Cole, Neeraj Dhar, Claudia Sala, 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

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

Jeffrey Alan Hubbell, Melody Swartz, Cyntia De Piano, Alexandre de Titta, Marie Ballester, Miriella Carmela Pasquier, Eleonora Simeoni, John McKinney, Neeraj Dhar

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

EspD Is Critical for the Virulence-Mediating ESX-1 Secretion System in Mycobacterium tuberculosis

Stewart Cole, Neeraj Dhar, Florence Pojer, Jeffrey Chen, Stefanie Boy-Röttger

ESAT-6 system 1 (ESX-1)-mediated secretion in Mycobacterium tuberculosis is dependent on proteins encoded by the cotranscribed espA-espC-espD gene cluster. While the roles of EspA and EspC with respect to the ESX-1 secretion system have been actively inves ...

American Society for Microbiology2011

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

Development of a repressible mycobacterial promoter system based on two transcriptional repressors

Stewart Cole, Neeraj Dhar, Claudia Sala

Tightly regulated gene expression systems represent invaluable tools for studying gene function and for the validation of drug targets in bacteria. While several regulated bacterial promoters have been characterized, few of them have been successfully used ...

Oxford University Press2010

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

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

Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis

John McKinney, Stewart Cole, Neeraj Dhar, Claudia Sala, Elizabeth Fullam, Giulia Manina

New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in ...

American Association for the Advancement of Science2009

Enhanced and Enduring Protection against Tuberculosis by Recombinant BCG-Ag85C and Its Association with Modulation of Cytokine Profile in Lung

Neeraj Dhar

Background: The variable efficacy (0-80%) of Mycobacterium bovis Bacille Calmette Gurein (BCG) vaccine against adult tuberculosis (TB) necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG) over-expressing promisi ...

Public Library of Science2008

Microbial phenotypic heterogeneity and antibiotic tolerance

John McKinney, Neeraj Dhar

Phenotypic heterogeneity, defined as metastable variation in cellular parameters generated by epigenetic mechanisms, is crucial for the persistence of bacterial populations under fluctuating selective pressures. Diversity ensures that some individuals will ...

2007

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