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ORIGINAL RESEARCH article

Front. Mol. Biosci.

Sec. Cellular Biochemistry

Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1613454

This article is part of the Research TopicUnraveling Enzyme-Substrate Dynamics in Protein Acylation and Disease ImplicationsView all 3 articles

Insights into the protein ubiquitinome in the host-pathogen interplay during Mycobacterium tuberculosis infection

Provisionally accepted
  • 1National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, China
  • 2Shenzhen Baoan People's Hospital, Shenzhen, Guangdong Province, China
  • 3Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China

The final, formatted version of the article will be published soon.

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), capable of manipulating and circumventing the host's immune system to establish infection.Ubiquitination plays a crucial role in the host's response to pathogens; however, the global alterations in protein ubiquitination during Mtb infection remain poorly understood. To elucidate the regulatory roles of ubiquitination in the immune response to Mtb, we investigated the ubiquitome of human macrophages following Mtb infection.In our study, we identified a total of 1,618 proteins exhibiting altered ubiquitination levels, with 1,182 lysine-ubiquitination sites in 828 proteins showing increased ubiquitination and 1,077 sites in 790 proteins displaying decreased ubiquitination.Bioinformatics analyses revealed that most proteins involved in the immune response were upregulated, including those associated with autophagy, lysosome, the NF-κB signaling pathway, necroptosis, and ferroptosis. Furthermore, the ubiquitination levels of numerous proteins involved in conserved physiological processes, such as ribosome biogenesis, spliceosome function, nucleocytoplasmic transport, and mRNA surveillance, were also altered, suggesting that these pathways may be regulated by ubiquitination during Mtb infection. The extensive pool of ubiquitinated proteins and sites identified in this study will serve as a valuable resource for understanding the regulatory mechanisms of the ubiquitination system in immune responses during Mtb infection.

Keywords: Mycobacterium tuberculosis, macrophage, host-pathogen interaction, Ubiquitinome, immune response

Received: 17 Apr 2025; Accepted: 08 Aug 2025.

Copyright: © 2025 Zhang, Feng, Lin, Hang, Li, Xu and Ye. 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: Guoliang Zhang, National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, China

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