Immunoreactive Proteins of Dormant Mycobacterium tuberculosis Cells

Трутнева, К. А.; Авдиенко, В. Г.; Demina, Galina R.; Shleeva, Margarita O.; Шумков, М. С.; Salina, Elena G.; Kaprelyants, Arseny S.

doi:10.1134/s0003683821020174

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…Among 62 seropositive TB proteins reported by Zhou et al, 12 proteins out of 40 were found in the current study. Additionally, experiments recently carried out on the sera of 42 TB patients allowed the detection of a set of 27 potentially immunoreactive proteins [ 85 ], six of them ( Rv2623 , Rv2018 , Rv2145c , Rv2744c , Rv1837c , Rv0341 ) similarly detected in the current study with a positive FC in the dormant state. It is to be anticipated that the list of selected antigenic proteins includes those that may be of interest for identifying the specific ‘immunosignature’ of latent TB, which can later be used for immunodiagnosis of latent TB.…”

Section: Discussionmentioning

confidence: 69%

Shotgun proteomic profiling of dormant, ‘non-culturable’ Mycobacterium tuberculosis

et al. 2022

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Dormant cells of Mycobacterium tuberculosis, in addition to low metabolic activity and a high level of drug resistance, are characterized by ‘non-culturability’–a specific reversible state of the inability of the cells to grow on solid media. The biochemical characterization of this physiological state of the pathogen is only superficial, pending clarification of the metabolic processes that may exist in such cells. In this study, applying LC-MS proteomic profiling, we report the analysis of proteins accumulated in dormant, ‘non-culturable’ M. tuberculosis cells in an in vitro model of self-acidification of mycobacteria in the post-stationary phase, simulating the in vivo persistence conditions—the raw data are available via ProteomeXchange with identifier PXD028849. This approach revealed the preservation of 1379 proteins in cells after 5 months of storage in dormancy; among them, 468 proteins were statistically different from those in the actively growing cells and bore a positive fold change (FC). Differential analysis revealed the proteins of the pH-dependent regulatory system PhoP and allowed the reconstruction of the reactions of central carbon/glycerol metabolism, as well as revealing the salvaged pathways of mycothiol and UMP biosynthesis, establishing the cohort of survival enzymes of dormancy. The annotated pathways mirror the adaptation of the mycobacterial metabolic machinery to life within lipid-rich macrophages: especially the involvement of the methyl citrate and glyoxylate pathways. Thus, the current in vitro model of M. tuberculosis self-acidification reflects the biochemical adaptation of these bacteria to persistence in vivo. Comparative analysis with published proteins displaying antigenic properties makes it possible to distinguish immunoreactive proteins among the proteins bearing a positive FC in dormancy, which may include specific antigens of latent tuberculosis. Additionally, the biotransformatory enzymes (oxidoreductases and hydrolases) capable of prodrug activation and stored up in the dormant state were annotated. These findings may potentially lead to the discovery of immunodiagnostic tests for early latent tuberculosis and trigger the discovery of efficient drugs/prodrugs with potency against non-replicating, dormant populations of mycobacteria.

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Section: Discussionmentioning

confidence: 69%

Shotgun proteomic profiling of dormant, ‘non-culturable’ Mycobacterium tuberculosis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Among 62 seropositive TB proteins reported by Zhou et al, 12 proteins out of 40 were found in the current study. Additionally, experiments recently carried out on the sera of 42 TB patients allowed the detection of a set of 27 potentially immunoreactive proteins (74), six of them (Rv2623, Rv2018, Rv2145c, Rv2744c, Rv1837c, Rv0341) similarly detected in the curent study with a positive FC in the dormant state. It is to be anticipated that the list of selected antigenic proteins includes those that may be of interest for identifying the specific 'immunosignature' of latent TB, which can later be used for immunodiagnosis of latent TB.…”

Section: The High-throughput Lc-ms-based Reconstruction Of Central Carbon Metabolism Significantlymentioning

confidence: 99%

Shotgun proteomic profiling of dormant, ‘non-culturable’Mycobacterium tuberculosis

Nikitushkin

Shleeva

Loginov

et al. 2021

Preprint

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Dormant cells of Mycobacterium tuberculosis, in addition to low metabolic activity and a high level of drug resistance, are characterized by 'non-culturability' – a state of the inability of the cells to grow on solid media. In this study, applying LC-MS proteomic profiling, we report the analysis of proteins accumulated in dormant, 'non-culturable' M. tuberculosis cells in a model of self-acidification of mycobacteria in the post-stationary phase, simulating the in vivo persistence conditions. This approach revealed the accumulation of a significant number of proteins after 4 months of storage in dormancy; among them, 468 proteins were significantly different from those in the actively growing cells and bore a positive fold change. Differential analysis revealed the proteins of the pH-dependent regulatory system phoP and allowed the reconstruction of the reactions of central carbon/glycerol metabolism, as well as revealing the salvaged pathways of mycothiol and UMP biosynthesis, establishing the cohort of survival enzymes of dormancy. The annotated pathways mirror the adaptation of the mycobacterial metabolic machinery to life within lipid-rich macrophages, especially the involvement of the methyl citrate and glyoxylate pathways. Thus, the current model of M. tuberculosis reflects the biochemical adaptation of these bacteria to persistence in vivo. Comparative analysis with published proteins with antigenic properties makes it possible to distinguish immunoreactive proteins among the proteins bearing a positive FC, which may include specific antigens of latent tuberculosis. Additionally, the biotransformatory enzymes (oxidoreductases and hydrolases) capable of prodrug activation and stored in the dormant state were annotated.

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Immunoreactive Proteins of Dormant Mycobacterium tuberculosis Cells

Cited by 2 publications

References 21 publications

Shotgun proteomic profiling of dormant, ‘non-culturable’ Mycobacterium tuberculosis

Shotgun proteomic profiling of dormant, ‘non-culturable’ Mycobacterium tuberculosis

Shotgun proteomic profiling of dormant, ‘non-culturable’Mycobacterium tuberculosis

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