Publications by Jérémie Piton

Structural and DNA binding properties of mycobacterial integration host factor mIHF

Giovanni Dietler, Stewart Cole, Aleksandre Japaridze, Rajkumar Singh, Luciano Andres Abriata, Nina Theres Odermatt, Jérémie Piton, David Lyndon Emsley, Moreno Lelli

In bacteria, nucleoid associated proteins (NAPs) take part in active chromosome organization by supercoil management, three-dimensional DNA looping and direct transcriptional control. Mycobacterial integration host factor (mIHF, rv1388) is a NAP restricted ...

Elsevier2020

6,11-Dioxobenzo[f]pyrido[1,2-a]indoles Kill Mycobacterium tuberculosis by Targeting Iron-Sulfur Protein Rv0338c (IspQ), A Putative Redox Sensor

Kai Johnsson, Stewart Cole, Monica Rengifo Gonzalez, Edina Rita Székely, Andrej Benjak, Jérémie Piton

Screening of a diversity-oriented compound library led to the identification of two 6,11-dioxobenzo[f]pyrido[1,2-a]indoles (DBPI) that displayed low micromolar bactericidal activity against the Erdman strain of Mycobacterium tuberculosis in vitro. The acti ...

AMER CHEMICAL SOC2020

High resolution CryoEM structure of the ring-shaped virulence factor EspB from Mycobacterium tuberculosis

Stewart Cole, Florence Pojer, Jérémie Piton

The EspB protein of Mycobacterium tuberculosis is a 60 kDa virulence factor, implicated in conjugation and exported by the ESX-1 system of which it may also be a component. Previous attempts to obtain high-resolution maps of EspB by cryo-electron microscop ...

2020

Polarly Localized EccE(1) Is Required for ESX-1 Function and Stabilization of ESX-1 Membrane Proteins in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Ming Zhang, Jérémie Piton, Paloma Julia Soler Arnedo

Mycobacterium tuberculosis is a slow-growing intracellular bacterium with the ability to induce host cell death and persist indefinitely in the human body. This pathogen uses the specialized ESX-1 secretion system to secrete virulence factors and potent im ...

American Society for Microbiology2020

New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosis

Stewart Cole, Shi-Yan Caroline Foo, Anthony Vocat, Andrej Benjak, Jérémie Piton, Andréanne Lupien

The emergence of multi-drug (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB) is a major threat to the global management of tuberculosis (TB) worldwide. New chemical entities are of need to treat drug-resistant TB. In this study, the mode of ac ...

2020

The Exchangeable Apolipoprotein Nplp2 Sustains Lipid Flow and Heat Acclimation in Drosophila

Jean Philippe Boquete, Bruno Lemaitre, Jérémie Piton, Samuel Rommelaere

In ectotherms, increased ambient temperature requires the organism to consume substantial amounts of energy to sustain a higher metabolic rate, prevent cellular damage, and respond to heat stress. Here, we identify a heat-inducible apolipoprotein required ...

2019

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

Arylvinylpiperazine Amides, a New Class of Potent Inhibitors Targeting QcrB of Mycobacterium tuberculosis

Stewart Cole, Raphael Christopher Sommer, Shi-Yan Caroline Foo, Anthony Vocat, Andrej Benjak, Jérémie Piton, Andréanne Lupien

New drugs are needed to control the current tuberculosis (TB) pandemic caused by infection with Mycobacterium tuberculosis. We report here on our work with AX-35, an arylvinylpiperazine amide, and four related analogs, which are potent antitubercular agent ...

AMER SOC MICROBIOLOGY2018

Structure-Based Drug Design and Characterization of Sulfonyl-Piperazine Benzothiazinone Inhibitors of DprE1 from Mycobacterium tuberculosis

Stewart Cole, Shi-Yan Caroline Foo, Anthony Vocat, Jérémie Piton, Andréanne Lupien

Macozinone (MCZ) is a tuberculosis (TB) drug candidate that specifically targets the essential flavoenzyme DprE1, thereby blocking synthesis of the cell wall precursor decaprenyl phosphoarabinose (DPA) and provoking lysis of Mycobacterium tuberculosis. As ...

AMER SOC MICROBIOLOGY2018

Distribution of the ribosome associated endonuclease Rae1 and the potential role of conserved amino acids in codon recognition

Jérémie Piton

We recently identified a novel ribonuclease in Bacillus subtilis called Rae1 that cleaves mRNAs in a translation-dependent manner. Rae1 is a member of the NYN/PIN family of ribonucleases and is highly conserved in the Firmicutes, the Cyanobacteria and the ...

TAYLOR & FRANCIS INC2018

Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases

Stewart Cole, Philippe Busso, Pushpendra Singh, Chloé Marie Loiseau, Andrej Benjak, Charlotte Avanzi, Jérémie Piton

Background Since leprosy is both treated and controlled by multidrug therapy (MDT) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy. All three obj ...

Public Library Science2017

Rae1/YacP, a new endoribonuclease involved in ribosome-dependent mRNA decay in Bacillus subtilis

Jérémie Piton

The PIN domain plays a central role in cellular RNA biology and is involved in processes as diverse as rRNA maturation, mRNA decay and telomerase function. Here, we solve the crystal structure of the Rae1 (YacP) protein of Bacillus subtilis, a founding mem ...

Wiley2017

Structural studies of Mycobacterium tuberculosis DprE1 interacting with its inhabitors

Stewart Cole, Shi-Yan Caroline Foo, Jérémie Piton

The flavoenzyme DprEl catalyses a crucial step in arabinan production for cell wall biosynthesis in Mycobacterium tuberculosis and is a highly vulnerable drug target. It was first discovered using benzothiazinones (BTZ): exquisitely potent bactericidal age ...

Elsevier Sci Ltd2017

Red squirrels in the British Isles are infected with leprosy bacilli

Stewart Cole, Philippe Busso, Chloé Marie Loiseau, Andrej Benjak, Charlotte Avanzi, Jérémie Piton

Leprosy, caused by infection with Mycobacterium leprae or the recently discovered Mycobacterium lepromatosis, was once endemic in humans in the British Isles. Red squirrels in Great Britain (Sciurus vulgaris) have increasingly been observed with leprosy-li ...

American Association for the Advancement of Science2016

Genomic and transcriptomic analysis of the streptomycin-dependent Mycobacterium tuberculosis strain 18b

Stewart Cole, Claudia Sala, Swapna Uplekar, Ming Zhang, Andrej Benjak, Jérémie Piton

Background: The ability of Mycobacterium tuberculosis to establish a latent infection (LTBI) in humans confounds the treatment of tuberculosis. Consequently, there is a need to discover new therapeutic agents that can kill M. tuberculosis both during activ ...

2016

Characterization of DprE1-Mediated Benzothiazinone Resistance in Mycobacterium tuberculosis

Gaëlle Séraphine Kolly, Stewart Cole, Claudia Sala, Benoit Lechartier, Joao Pedro De Almeida Neres, Stefanie Boy-Röttger, Jan Lars Rybniker, Shi-Yan Caroline Foo, Jérémie Piton, Andréanne Lupien

Benzothiazinones (BTZs) are a class of compounds found to be extremely potent against both drug-susceptible and drug-resistant Mycobacterium tuberculosis strains. The potency of BTZs is explained by their specificity for their target decaprenylphosphoryl-D ...

American Society for Microbiology2016

Structure of EspB, a secreted substrate of the ESX-1 secretion system of Mycobacterium tuberculosis

Stewart Cole, Florence Pojer, Aleksandre Japaridze, Jérémie Piton

Mycobacterium tuberculosis secretes multiple virulence factors during infection via the general Sec and Tat pathways, and via specialized ESX secretion systems, also referred to as type VII secretion systems. The ESX-1 secretion system is an important viru ...

Elsevier2015

The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis

Gaëlle Séraphine Kolly, Stewart Cole, Ruben Hartkoorn, Joao Pedro De Almeida Neres, Anthony Vocat, Trent Michael Conroy, Jérémie Piton

8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-beta-D-ribose 2'-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. Structure-activity relationship (SAR) studie ...

American Society for Microbiology2015