Publications by Swapna Uplekar

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

Cross-Resistance between Clofazimine and Bedaquiline through Upregulation of MmpL5 in Mycobacterium tuberculosis

Stewart Cole, Swapna Uplekar, Ruben Hartkoorn

The antileprosy drug clofazimine is also of interest for the treatment of multidrug-resistant tuberculosis. To understand possible resistance mechanisms, clofazimine-resistant Mycobacterium tuberculosis mutants were isolated in vitro, and, unexpectedly, fo ...

Amer Soc Microbiology2014

The PhoP-Dependent ncRNA Mcr7 Modulates the TAT Secretion System in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Swapna Uplekar, Jacques Rougemont, Andrej Benjak

The PhoPR two-component system is essential for virulence in Mycobacterium tuberculosis where it controls expression of approximately 2% of the genes, including those for the ESX-1 secretion apparatus, a major virulence determinant. Mutations in phoP lead ...

Public Library of Science2014

High-resolution transcriptome and genome-wide dynamics of RNA polymerase and NusA in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Swapna Uplekar, Jacques Rougemont

To construct a regulatory map of the genome of the human pathogen, Mycobacterium tuberculosis, we applied two complementary high-resolution approaches: strand-specific RNA-seq, to survey the global transcriptome, and ChIP-seq, to monitor the genome-wide dy ...

Oxford University Press2013

High-resolution detection of DNA binding sites of the global transcriptional regulator GlxR in Corynebacterium glutamicum

Stewart Cole, Claudia Sala, Swapna Uplekar

The transcriptional regulator GlxR has been characterized as a global hub within the gene-regulatory network of Corynebacterium glutamicum. Chromatin immunoprecipitation with a specific anti-GlxR antibody and subsequent high-throughput sequencing (ChIP-seq ...

Soc General Microbiology2013

Genomics and transcriptomics of the Mycobacterium tuberculosis complex

Swapna Uplekar

The goal of eliminating tuberculosis (TB) by 2050 depends on the development of improved TB diagnostics, drugs and vaccines. Advances in these areas require a deep understanding of the disease and its causative agent, Mycobacterium tuberculosis (M. tb). My ...

EPFL2012

Virulence Regulator EspR of Mycobacterium tuberculosis Is a Nucleoid-Associated Protein

Benjamin Blasco, Stewart Cole, Claudia Sala, Florence Pojer, Jeffrey Chen, Swapna Uplekar, Jacques Rougemont, Ruben Hartkoorn

The principal virulence determinant of Mycobacterium tuberculosis (Mtb), the ESX-1 protein secretion system, is positively controlled at the transcriptional level by EspR. Depletion of EspR reportedly affects a small number of genes, both positively or neg ...

Public Library of Science2012

A Point Mutation in cycA Partially Contributes to the D-cycloserine Resistance Trait of Mycobacterium bovis BCG Vaccine Strains

Stewart Cole, Jeffrey Chen, Swapna Uplekar

In mycobacteria, CycA a D-serine, L-and D-alanine, and glycine transporter also functions in the uptake of D-cycloserine, an important second-line anti-tubercular drug. A single nucleotide polymorphism identified in the cycA gene of BCG was hypothesized to ...

Public Library of Science2012

Genome-Wide Definition of the SigF Regulon in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Swapna Uplekar, Jacques Rougemont, Ruben Hartkoorn, Philippe Busso

In Mycobacterium tuberculosis the alternative sigma factor SigF controls the expression of a particular subset of genes by altering RNA polymerase specificity. Here, we utilize two genome-wide approaches to identify SigF-binding sites: chromatin immunoprec ...

American Society for Microbiology2012

Towards a new tuberculosis drug: pyridomycin - nature's isoniazid

Stewart Cole, Claudia Sala, Florence Pojer, Sophie Magnet, Swapna Uplekar, Ruben Hartkoorn, Joao Pedro De Almeida Neres, Raju Mukherjee

Tuberculosis, a global threat to public health, is becoming untreatable due to widespread drug resistance to frontline drugs such as the InhA-inhibitor isoniazid. Historically, by inhibiting highly vulnerable targets, natural products have been an importan ...

Wiley Open Access2012

Spontaneous phthiocerol dimycocerosate-deficient variants of Mycobacterium tuberculosis are susceptible to gamma interferon-mediated immunity

John McKinney, Anna De Graff Tischler, Swapna Uplekar

Onset of the adaptive immune response in mice infected with Mycobacterium tuberculosis is accompanied by slowing of bacterial replication and establishment of a chronic infection. Stabilization of bacterial numbers during the chronic phase of infection is ...

2011

Comparative genomics of Esx genes from clinical isolates of Mycobacterium tuberculosis provides evidence for gene conversion and epitope variation

Stewart Cole, Swapna Uplekar, Jacques Rougemont

The 23-membered Esx protein family is involved in the host-pathogen interactions of Mycobacterium tuberculosis. These secreted proteins are among the most immunodominant antigens recognized by the human immune system and have thus been used to develop vacc ...

2011

Primer-initiated sequence synthesis to detect and assemble structural variants

Carine Delattre-Gubelmann, Stewart Cole, Swapna Uplekar, Bart Deplancke, Jacques Rougemont, Andreas Massouras, Frederik Decouttere

Nature Publishing Group2010

A comprehensive survey of single nucleotide polymorphisms (SNPs) across Mycobacterium bovis strains and M. bovis BCG vaccine strains refines the genealogy and defines a minimal set of SNPs that separate virulent M. bovis strains and M. bovis BCG strains

Stewart Cole, Swapna Uplekar

To further unravel the mechanisms responsible for attenuation of the tuberculosis vaccine Mycobacterium bovis BCG, comparative genomics was used to identify single nucleotide polymorphisms (SNPs) that differed between sequenced strains of Mycobacterium bov ...

2009