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RNA Sequencing of macrophages harboring redox-diverse Mycobacterium tuberculosis.

ABSTRACT: RNA Sequencing of macrophages harboring redox-diverse Mycobacterium tuberculosis.

PROVIDER: PRJNA1195004 | ENA |

REPOSITORIES: ENA

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RNA Sequencing of macrophages harboring redox-diverse Mycobacterium tuberculosis.

Project description:The ability of Mycobacterium tuberculosis (Mtb) to tolerate antibiotics is a major impediment in the treatment of tuberculosis. This antibiotic tolerance is influenced by the host cells in which the bacteria reside, as Mtb senses host cues, and the bacterial response can provide an enhanced ability to withstand anti-TB drugs. Previouslyt, we have shown that Mtb exhibits redox heterogeneity in terms of its mycothiol redox potential (EMSH) giving rise to three broad subpopulations EMSH-reduced, EMSH-basal, and EMSH-oxidized Mtb specifically inside the macrophages. Among these, the EMSH-reduced Mtb exhibit enahnced tolerance to several anti-TB drugs while the EMSH-basal and EMSH-oxidized subpopulations are more susceptible. In this study, we explored the transcriptomic level differences between macrophages that harbor the antibiotic tolerant Mtb and those harboring antibiotic susceptible Mtb to get a mechanistic understanding of host factors that influence drug tolerance in intracellular Mtb.

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Project description:<p><em>Mycobacterium tuberculosis</em> (Mtb), the cause of tuberculosis, kills over one million people worldwide each year. Mtb is classified into ten distinct lineages, each harboring unique genetic changes that influence its survival, virulence, and transmissibility. Although metabolism plays a critical role in Mtb infection and persistence, the metabolomic profiles of different Mtb lineages remain poorly characterized. Here, by using metabolomic and bioinformatic approaches, we have determined the metabolome of representative strains belonging to three main lineages, namely lineage 1, lineage 2 and lineage 4. We show that the ancient lineage 1 has considerable differences in its metabolome compared to lineages 2 and 4. Those differences are mainly related to amino acids, peptidoglycan synthesis intermediates and ergothioneine, a sulphur-containing histidine derivative with potent antioxidant and redox properties. Taken together, these data represent the first comprehensive analysis of the metabolome of three main Mtb lineages.</p>

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Project description:Pfkfb1 Selectively Identifies Macrophages Harboring Intracellular Growing Bacteria

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