Differential genome organization revealed by comparative topological analysis of Mycobacterium tuberculosis strains H37Rv and H37Ra
ABSTRACT Recent studies have shown that three-dimensional architecture of bacterial chromatin plays an important role in gene expression regulation. However, genome topological organization in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, remains unknown. On the other hand, the ex...
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American Society for Microbiology
2025-05-01
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| Series: | mSystems |
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| Online Access: | https://journals.asm.org/doi/10.1128/msystems.00562-24 |
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| author | Mohit Mishra Ajay Arya Md. Zubbair Malik Akanksha Mishra Seyed E. Hasnain Rakesh Bhatnagar Shandar Ahmad Rupesh Chaturvedi |
| author_facet | Mohit Mishra Ajay Arya Md. Zubbair Malik Akanksha Mishra Seyed E. Hasnain Rakesh Bhatnagar Shandar Ahmad Rupesh Chaturvedi |
| author_sort | Mohit Mishra |
| collection | DOAJ |
| description | ABSTRACT Recent studies have shown that three-dimensional architecture of bacterial chromatin plays an important role in gene expression regulation. However, genome topological organization in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, remains unknown. On the other hand, the exact mechanism of differential pathogenesis in the canonical strains of M. tuberculosis H37Rv and H37Ra remains poorly understood in terms of their raw sequences. In this context, a detailed contact map from a Hi-C experiment is a candidate for what bridges the gap. Here, we present the first comprehensive report on genome-wide contact maps between regions of H37Rv and H37Ra genomes. We tracked differences between the genome architectures of H37Rv and H37Ra, which could possibly explain the virulence attenuation in H37Ra. We confirm the existence of a differential organization between the two strains most significantly a higher chromosome interaction domain (CID) size in the attenuated H37Ra strain. CID boundaries are also found enriched with highly expressed genes and with higher operon density in H37Rv. Furthermore, most of the differentially expressed PE/PPE genes were present near the CID boundaries in H37Rv and not in H37Ra. We also found a systemic reorganization of CIDs in both virulent H37Rv and avirulent H37Ra strains after hypoxia induction. Collectively, our study proposes a differential genomic topological pattern between H37Rv and H37Ra, which could explain the virulence attenuation in H37Ra.IMPORTANCEGenome organization studies using chromosome conformation capture techniques have proved to be useful in establishing a three-dimensional (3D) landscape of bacterial chromatin. The sequence-based studies failed to unveil the exact mechanism for virulence attenuation in one of the Mycobacterium tuberculosis strains H37Ra. Moreover, as of today, no study investigated the 3D structure of the M. tuberculosis genome and how 3D genome organization affects transcription in M. tuberculosis. We investigated the genome topology in virulent and attenuated strains of M. tuberculosis using Hi-C. Our study demonstrated that virulent and attenuated M. tuberculosis strains exhibit distinct topological features that correlate with higher gene expression of virulence genes in the virulent H37Rv strain. |
| format | Article |
| id | doaj-art-70f2f2b4798c42698c04e292dfef1b89 |
| institution | Kabale University |
| issn | 2379-5077 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | American Society for Microbiology |
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| series | mSystems |
| spelling | doaj-art-70f2f2b4798c42698c04e292dfef1b892025-08-20T03:54:01ZengAmerican Society for MicrobiologymSystems2379-50772025-05-0110510.1128/msystems.00562-24Differential genome organization revealed by comparative topological analysis of Mycobacterium tuberculosis strains H37Rv and H37RaMohit Mishra0Ajay Arya1Md. Zubbair Malik2Akanksha Mishra3Seyed E. Hasnain4Rakesh Bhatnagar5Shandar Ahmad6Rupesh Chaturvedi7School of Biotechnology, Jawaharlal Nehru University, New Delhi, IndiaSchool of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, IndiaSchool of Biotechnology, Jawaharlal Nehru University, New Delhi, IndiaSchool of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, IndiaDepartment of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, IndiaAmity University, Jaipur, Rajasthan, IndiaSchool of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, IndiaSchool of Biotechnology, Jawaharlal Nehru University, New Delhi, IndiaABSTRACT Recent studies have shown that three-dimensional architecture of bacterial chromatin plays an important role in gene expression regulation. However, genome topological organization in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, remains unknown. On the other hand, the exact mechanism of differential pathogenesis in the canonical strains of M. tuberculosis H37Rv and H37Ra remains poorly understood in terms of their raw sequences. In this context, a detailed contact map from a Hi-C experiment is a candidate for what bridges the gap. Here, we present the first comprehensive report on genome-wide contact maps between regions of H37Rv and H37Ra genomes. We tracked differences between the genome architectures of H37Rv and H37Ra, which could possibly explain the virulence attenuation in H37Ra. We confirm the existence of a differential organization between the two strains most significantly a higher chromosome interaction domain (CID) size in the attenuated H37Ra strain. CID boundaries are also found enriched with highly expressed genes and with higher operon density in H37Rv. Furthermore, most of the differentially expressed PE/PPE genes were present near the CID boundaries in H37Rv and not in H37Ra. We also found a systemic reorganization of CIDs in both virulent H37Rv and avirulent H37Ra strains after hypoxia induction. Collectively, our study proposes a differential genomic topological pattern between H37Rv and H37Ra, which could explain the virulence attenuation in H37Ra.IMPORTANCEGenome organization studies using chromosome conformation capture techniques have proved to be useful in establishing a three-dimensional (3D) landscape of bacterial chromatin. The sequence-based studies failed to unveil the exact mechanism for virulence attenuation in one of the Mycobacterium tuberculosis strains H37Ra. Moreover, as of today, no study investigated the 3D structure of the M. tuberculosis genome and how 3D genome organization affects transcription in M. tuberculosis. We investigated the genome topology in virulent and attenuated strains of M. tuberculosis using Hi-C. Our study demonstrated that virulent and attenuated M. tuberculosis strains exhibit distinct topological features that correlate with higher gene expression of virulence genes in the virulent H37Rv strain.https://journals.asm.org/doi/10.1128/msystems.00562-24M. tuberculosisHi-CCIDCID boundariesgene expression |
| spellingShingle | Mohit Mishra Ajay Arya Md. Zubbair Malik Akanksha Mishra Seyed E. Hasnain Rakesh Bhatnagar Shandar Ahmad Rupesh Chaturvedi Differential genome organization revealed by comparative topological analysis of Mycobacterium tuberculosis strains H37Rv and H37Ra mSystems M. tuberculosis Hi-C CID CID boundaries gene expression |
| title | Differential genome organization revealed by comparative topological analysis of Mycobacterium tuberculosis strains H37Rv and H37Ra |
| title_full | Differential genome organization revealed by comparative topological analysis of Mycobacterium tuberculosis strains H37Rv and H37Ra |
| title_fullStr | Differential genome organization revealed by comparative topological analysis of Mycobacterium tuberculosis strains H37Rv and H37Ra |
| title_full_unstemmed | Differential genome organization revealed by comparative topological analysis of Mycobacterium tuberculosis strains H37Rv and H37Ra |
| title_short | Differential genome organization revealed by comparative topological analysis of Mycobacterium tuberculosis strains H37Rv and H37Ra |
| title_sort | differential genome organization revealed by comparative topological analysis of mycobacterium tuberculosis strains h37rv and h37ra |
| topic | M. tuberculosis Hi-C CID CID boundaries gene expression |
| url | https://journals.asm.org/doi/10.1128/msystems.00562-24 |
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