MTS1338, A Small Mycobacterium tuberculosis RNA, Regulates Transcriptional Shifts Consistent With Bacterial Adaptation for Entering Into Dormancy and Survival Within Host Macrophages

Small non-coding RNAs play a significant role in bacterial adaptation to changing environmental conditions. We investigated the dynamics of expression of MTS1338, a small non-coding RNA of Mycobacterium tuberculosis, in the mouse model in vivo, regulation of its expression in the infected macrophage...

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Main Authors: Elena G. Salina, Artem Grigorov, Yulia Skvortsova, Konstantin Majorov, Oksana Bychenko, Albina Ostrik, Nadezhda Logunova, Dmitriy Ignatov, Arseny Kaprelyants, Alexander Apt, Tatyana Azhikina
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-11-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/article/10.3389/fcimb.2019.00405/full
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author Elena G. Salina
Artem Grigorov
Yulia Skvortsova
Konstantin Majorov
Oksana Bychenko
Albina Ostrik
Nadezhda Logunova
Dmitriy Ignatov
Arseny Kaprelyants
Alexander Apt
Tatyana Azhikina
author_facet Elena G. Salina
Artem Grigorov
Yulia Skvortsova
Konstantin Majorov
Oksana Bychenko
Albina Ostrik
Nadezhda Logunova
Dmitriy Ignatov
Arseny Kaprelyants
Alexander Apt
Tatyana Azhikina
author_sort Elena G. Salina
collection DOAJ
description Small non-coding RNAs play a significant role in bacterial adaptation to changing environmental conditions. We investigated the dynamics of expression of MTS1338, a small non-coding RNA of Mycobacterium tuberculosis, in the mouse model in vivo, regulation of its expression in the infected macrophages, and the consequences of its overexpression in bacterial cultures. Here we demonstrate that MTS1338 significantly contributes to host-pathogen interactions. Activation of the host immune system triggered NO-inducible up-regulation of MTS1338 in macrophage-engulfed mycobacteria. Constitutive overexpression of MTS1338 in cultured mycobacteria improved their survival in vitro under low pH conditions. MTS1338 up-regulation launched a spectrum of shifts in the transcriptome profile similar to those reported for M. tuberculosis adaptation to hostile intra-macrophage environment. Using the RNA-seq approach, we demonstrate that gene expression changes accompanying MTS1338 overexpression indicate reduction in translational activity and bacterial growth. These changes indicate mycobacteria entering the dormant state. Taken together, our results suggest a direct involvement of this sRNA in the interplay between mycobacteria and the host immune system during infectious process.
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spelling doaj.art-cfc6724d335d456ca90af3f7ffc1c6ee2022-12-21T18:49:55ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882019-11-01910.3389/fcimb.2019.00405501725MTS1338, A Small Mycobacterium tuberculosis RNA, Regulates Transcriptional Shifts Consistent With Bacterial Adaptation for Entering Into Dormancy and Survival Within Host MacrophagesElena G. Salina0Artem Grigorov1Yulia Skvortsova2Konstantin Majorov3Oksana Bychenko4Albina Ostrik5Nadezhda Logunova6Dmitriy Ignatov7Arseny Kaprelyants8Alexander Apt9Tatyana Azhikina10Laboratory of Biochemistry of Stresses in Microorganisms, Bach Institute of Biochemistry, Research Center of Biotechnology, Moscow, RussiaLaboratory of Regulatory Transcriptomics, Department of Genomics and Postgenomic Technologies, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, RussiaLaboratory of Regulatory Transcriptomics, Department of Genomics and Postgenomic Technologies, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, RussiaLaboratory for Immunogenetics, Department of Immunology, Central Institute for Tuberculosis, Moscow, RussiaLaboratory of Regulatory Transcriptomics, Department of Genomics and Postgenomic Technologies, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, RussiaLaboratory of Biochemistry of Stresses in Microorganisms, Bach Institute of Biochemistry, Research Center of Biotechnology, Moscow, RussiaLaboratory for Immunogenetics, Department of Immunology, Central Institute for Tuberculosis, Moscow, RussiaLaboratory of Regulatory Transcriptomics, Department of Genomics and Postgenomic Technologies, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, RussiaLaboratory of Biochemistry of Stresses in Microorganisms, Bach Institute of Biochemistry, Research Center of Biotechnology, Moscow, RussiaLaboratory for Immunogenetics, Department of Immunology, Central Institute for Tuberculosis, Moscow, RussiaLaboratory of Regulatory Transcriptomics, Department of Genomics and Postgenomic Technologies, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, RussiaSmall non-coding RNAs play a significant role in bacterial adaptation to changing environmental conditions. We investigated the dynamics of expression of MTS1338, a small non-coding RNA of Mycobacterium tuberculosis, in the mouse model in vivo, regulation of its expression in the infected macrophages, and the consequences of its overexpression in bacterial cultures. Here we demonstrate that MTS1338 significantly contributes to host-pathogen interactions. Activation of the host immune system triggered NO-inducible up-regulation of MTS1338 in macrophage-engulfed mycobacteria. Constitutive overexpression of MTS1338 in cultured mycobacteria improved their survival in vitro under low pH conditions. MTS1338 up-regulation launched a spectrum of shifts in the transcriptome profile similar to those reported for M. tuberculosis adaptation to hostile intra-macrophage environment. Using the RNA-seq approach, we demonstrate that gene expression changes accompanying MTS1338 overexpression indicate reduction in translational activity and bacterial growth. These changes indicate mycobacteria entering the dormant state. Taken together, our results suggest a direct involvement of this sRNA in the interplay between mycobacteria and the host immune system during infectious process.https://www.frontiersin.org/article/10.3389/fcimb.2019.00405/fullMycobacterium tuberculosistuberculosissmall RNA MTS1338RNA-seqinfection
spellingShingle Elena G. Salina
Artem Grigorov
Yulia Skvortsova
Konstantin Majorov
Oksana Bychenko
Albina Ostrik
Nadezhda Logunova
Dmitriy Ignatov
Arseny Kaprelyants
Alexander Apt
Tatyana Azhikina
MTS1338, A Small Mycobacterium tuberculosis RNA, Regulates Transcriptional Shifts Consistent With Bacterial Adaptation for Entering Into Dormancy and Survival Within Host Macrophages
Frontiers in Cellular and Infection Microbiology
Mycobacterium tuberculosis
tuberculosis
small RNA MTS1338
RNA-seq
infection
title MTS1338, A Small Mycobacterium tuberculosis RNA, Regulates Transcriptional Shifts Consistent With Bacterial Adaptation for Entering Into Dormancy and Survival Within Host Macrophages
title_full MTS1338, A Small Mycobacterium tuberculosis RNA, Regulates Transcriptional Shifts Consistent With Bacterial Adaptation for Entering Into Dormancy and Survival Within Host Macrophages
title_fullStr MTS1338, A Small Mycobacterium tuberculosis RNA, Regulates Transcriptional Shifts Consistent With Bacterial Adaptation for Entering Into Dormancy and Survival Within Host Macrophages
title_full_unstemmed MTS1338, A Small Mycobacterium tuberculosis RNA, Regulates Transcriptional Shifts Consistent With Bacterial Adaptation for Entering Into Dormancy and Survival Within Host Macrophages
title_short MTS1338, A Small Mycobacterium tuberculosis RNA, Regulates Transcriptional Shifts Consistent With Bacterial Adaptation for Entering Into Dormancy and Survival Within Host Macrophages
title_sort mts1338 a small mycobacterium tuberculosis rna regulates transcriptional shifts consistent with bacterial adaptation for entering into dormancy and survival within host macrophages
topic Mycobacterium tuberculosis
tuberculosis
small RNA MTS1338
RNA-seq
infection
url https://www.frontiersin.org/article/10.3389/fcimb.2019.00405/full
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