Publications de Neeraj Dhar | EPFL Graph Search

Investigating the composition and recruitment of the mycobacterial ImuA'-ImuB-DnaE2 mutasome

John McKinney, Neeraj Dhar, Zela Alexandria-Mae Martin

A DNA damage-inducible mutagenic gene cassette has been implicated in the emergence of drug resistance in Mycobacterium tuberculosis during anti-tuberculosis (TB) chemotherapy. However, the molecular composition and operation of the encoded 'mycobacterial ...

Elife Sciences Publ Ltd2023

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

Mechanopathology of biofilm-like Mycobacterium tuberculosis cords

Nicolas Jean Philippe Guex, Graham Knott, John McKinney, Neeraj Dhar, Jessica Sordet, Maxime Jan, Kunal Sharma, Mélanie Thérèse Marie Hannebelle, Vivek Vijay Thacker, Richa Mishra

Mycobacterium tuberculosis (Mtb) cultured axenically without detergent forms biofilm-like cords, a clinical identifier of virulence. In lung-on-chip (LoC) and mouse models, cords in alveolar cells contribute to suppression of innate immune signaling via nu ...

Cell Press2023

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

Mycobacterium tuberculosis EspK Has Active but Distinct Roles in the Secretion of EsxA and EspB

Neeraj Dhar

The Mycobacterium tuberculosis type-7 protein secretion system ESX-1 is a major driver of its virulence. While the functions of most ESX-1 components are characterized, many others remain poorly defined. In this study, we examined the role of EspK, an ESX- ...

American Society for Microbiology2022

Early invasion of the bladder wall by solitary bacteria protects UPEC from antibiotics and neutrophil swarms in an organoid model

Graham Knott, John McKinney, Neeraj Dhar, François Signorino-Gelo, Kunal Sharma, Vivek Vijay Thacker, Maria Clapés Cabrer

2021

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

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

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

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

Elicitation of efficient, protective immune responses by using DNA vaccines against tuberculosis (vol 23, pg 5655, 2005)

Neeraj Dhar

ELSEVIER SCI LTD2020

Bacteria: Driving polar growth

Neeraj Dhar

Profiling the phenotype of 200,000 mutants revealed a new cofactor that may help a group of rod-shaped bacteria elongate and grow. ...

2020

A lung-on-chip model of early Mycobacterium tuberculosis infection reveals an essential role for alveolar epithelial cells in controlling bacterial growth

John McKinney, Neeraj Dhar, Kunal Sharma, Vivek Vijay Thacker

We establish a murine lung-on-chip infection model and use time-lapse imaging to reveal the dynamics of host-Mycobacterium tuberculosis interactions at an air-liquid interface with a spatiotemporal resolution unattainable in animal models and to probe the ...

2020

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

Preexisting variation in DNA damage response predicts the fate of single mycobacteria under stress

John McKinney, Neeraj Dhar, Giulia Manina, Lalit Kumar Singh

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

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

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

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

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

An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division

Neeraj Dhar, Ashima Bhaskar, Dong Li

Mycobacteria possess a multi-layered cell wall that requires extensive remodelling during cell division. We investigated the role of an amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase, a peptidoglycan remodelling enzyme implicated in cell div ...

Nature Research2017

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