{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:43:28Z","timestamp":1788777808148,"version":"build-2803163510"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"This work was primarily supported by DST | Science and Engineering Research Board","award":["EMR\/2017\/005485"],"award-info":[{"award-number":["EMR\/2017\/005485"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2025,5,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Recent studies have shown that three-dimensional architecture of bacterial chromatin plays an important role in gene expression regulation. However, genome topological organization in\n              <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n              , the etiologic agent of tuberculosis, remains unknown. On the other hand, the exact mechanism of differential pathogenesis in the canonical strains of\n              <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n              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.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Genome 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\n                <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                strains H37Ra. Moreover, as of today, no study investigated the 3D structure of the\n                <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                genome and how 3D genome organization affects transcription in\n                <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                . We investigated the genome topology in virulent and attenuated strains of\n                <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                using Hi-C. Our study demonstrated that virulent and attenuated\n                <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                strains exhibit distinct topological features that correlate with higher gene expression of virulence genes in the virulent H37Rv strain.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msystems.00562-24","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T13:04:02Z","timestamp":1744031042000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Differential genome organization revealed by comparative topological analysis of\n            <i>Mycobacterium tuberculosis<\/i>\n            strains H37Rv and H37Ra"],"prefix":"10.1128","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-1440","authenticated-orcid":false,"given":"Mohit","family":"Mishra","sequence":"first","affiliation":[{"name":"School of Biotechnology, Jawaharlal Nehru University","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8864-9474","authenticated-orcid":false,"given":"Ajay","family":"Arya","sequence":"additional","affiliation":[{"name":"School of Computational and Integrative Sciences, Jawaharlal Nehru University","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6693-0401","authenticated-orcid":false,"given":"Md. Zubbair","family":"Malik","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Jawaharlal Nehru University","place":["New Delhi, India"]},{"name":"Department of Genetics and Bioinformatics, Dasman Diabetes Institute","place":["Dasman, Kuwait City, Kuwait"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akanksha","family":"Mishra","sequence":"additional","affiliation":[{"name":"School of Computational and Integrative Sciences, Jawaharlal Nehru University","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2967-0791","authenticated-orcid":true,"given":"Seyed E.","family":"Hasnain","sequence":"additional","affiliation":[{"name":"Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi","place":["New Delhi, India"]},{"name":"Department of Life Science, School of Basic Sciences and Research, Sharda University","place":["Greater Noida, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Amity University","place":["Jaipur, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7287-305X","authenticated-orcid":false,"given":"Shandar","family":"Ahmad","sequence":"additional","affiliation":[{"name":"School of Computational and Integrative Sciences, Jawaharlal Nehru University","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8219-8465","authenticated-orcid":true,"given":"Rupesh","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Jawaharlal Nehru University","place":["New Delhi, India"]},{"name":"Special Center for System Medicine, Jawaharlal Nehru University","place":["New Delhi, India"]},{"name":"Nanofluidiks Pvt. 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