ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Molecular Bacterial Pathogenesis
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1643664
Comparative Transcriptomic Signatures of Virulent and Attenuated Mycobacterium bovis Growing In vitro and In Mice
Provisionally accepted
- 1Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States
- 2Menoufia University Faculty of Computers & Information, Shebeen El-Kom, Egypt
- 3University of Wisconsin-Madison, Madison, United States
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Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), poses a significant global health and economic burden. Despite extensive research, a comprehensive understanding of M. bovis pathogenesis, particularly its transcriptional adaptation across different growth phases and within the host environment, remains incomplete. Here, we performed a comprehensive transcriptomic analysis of virulent M. bovis and the attenuated M. bovis BCG strain (BCG) across early-log, mid-log, and stationary growth phases to elucidate the molecular underpinnings of their phenotypic distinctions. RNA sequencing revealed distinct gene expression profiles, highlighting significant differences in pathways related to cell wall biosynthesis, lipid metabolism, transcriptional regulation, protein secretion, and the PE/PPE protein family. Notably, the virulent M. bovis exhibited an upregulation of virulence-associated genes, especially those involved in lipid metabolism and secretion systems, during the transition from early-and mid-log phases to the stationary phase. In contrast, BCG demonstrated an enrichment in stress response and metabolic adaptation pathways during the similar transition. Gene network analysis of differentially expressed genes (DEGs) provided a systems-level view of the transcriptional programs governing M. bovis and M. bovis BCG physiology, identifying five key modules of co-expressed genes that regulate small molecules transport, amino acid biosynthesis and immune evasion in M. bovis. Furthermore, we analyzed M. bovis transcriptional responses during murine lung infection, identifying a core set of DEGs linked to host-pathogen interactions and mechanisms of persistence. These findings offer novel insights into M. bovis adaptation strategies during survival under defined, in vitro growth conditions and highlight potential targets for improved vaccine design and therapeutic interventions following further analyses during host infection.
Keywords: M. bovis, Pathogenesis, Transcriptome (RNA-seq), comparative genomics, in vivo
Received: 09 Jun 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Abdelaal, Salem, Steinberg and Talaat. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Adel M Talaat, University of Wisconsin-Madison, Madison, United States
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