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

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_FF686038C606
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genomic and transcriptomic analysis of the streptomycin-dependent Mycobacterium tuberculosis strain 18b.
Périodique
BMC Genomics
Auteur⸱e⸱s
Benjak A., Uplekar S., Zhang M., Piton J., Cole S.T., Sala C.
ISSN
1471-2164 (Electronic)
ISSN-L
1471-2164
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
17
Pages
190
Langue
anglais
Résumé
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 active disease and LTBI. The streptomycin-dependent strain of M. tuberculosis, 18b, provides a useful tool for this purpose since upon removal of streptomycin (STR) it enters a non-replicating state that mimics latency both in vitro and in animal models.
The 4.41 Mb genome sequence of M. tuberculosis 18b was determined and this revealed the strain to belong to clade 3 of the ancient ancestral lineage of the Beijing family. STR-dependence was attributable to insertion of a single cytosine in the 530 loop of the 16S rRNA and to a single amino acid insertion in the N-terminal domain of initiation factor 3. RNA-seq was used to understand the genetic programme activated upon STR-withdrawal and hence to gain insight into LTBI. This revealed reconfiguration of gene expression and metabolic pathways showing strong similarities between non-replicating 18b and M. tuberculosis residing within macrophages, and with the core stationary phase and microaerophilic responses.
The findings of this investigation confirm the validity of 18b as a model for LTBI, and provide insight into both the evolution of tubercle bacilli and the functioning of the ribosome.

Mots-clé
Comparative Genomic Hybridization, Genome, Bacterial, High-Throughput Nucleotide Sequencing, INDEL Mutation, Models, Molecular, Molecular Sequence Annotation, Mycobacterium tuberculosis/classification, Mycobacterium tuberculosis/drug effects, Mycobacterium tuberculosis/genetics, Phylogeny, Polymorphism, Single Nucleotide, Protein Structure, Tertiary, RNA, Bacterial/genetics, RNA, Ribosomal, 16S/genetics, Ribosome Subunits, Small, Bacterial/genetics, Sequence Analysis, RNA, Streptomycin/pharmacology, Transcriptome
Pubmed
Web of science
Open Access
Oui
Création de la notice
04/04/2016 8:47
Dernière modification de la notice
20/08/2019 16:29
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