Dynamic Proteomic and PTMomic Characterization of Mycobacteria after Clinical Pharmaceutical Intervention
Tuberculosis, a major global health threat, necessitates understanding the pharmacological mechanisms of current drugs to combat multidrug resistance. In addition to alterations at the proteome level, the dynamic changes occurring at various levels of post-translational modifications (PTMs) following pharmacological intervention remain unclear. In our current study, we employed a quantitative proteomic approach to systematically analyze the dynamic molecular alterations at both the proteome and PTM levels in response to clinical drugs, including ethambutol, bedaquiline, moxifloxacin, and streptomycin. Our findings revealed enriched bioprocesses beyond known functions, phosphorylation-level changes in kinases and phosphatases, and increased acetylation levels with all four drugs. Overexpression of CobB in <i>Mycobacterium smegmatis</i> significantly increased its susceptibility to ethambutol, indicating enhanced drug sensitivity. Our study provides integrated multiomics resources for understanding the dynamic molecular characteristics and drug resistance associated with clinical drug interventions and proposes novel therapeutic strategies targeting the PTM levels.
Authors
- Lijie Tan
- Lu Zhou (ORCID: https://orcid.org/0000-0002-6807-2647)
- Hailong Jin (ORCID: https://orcid.org/0000-0002-2513-6540)
- Jun‐Yu Xu (ORCID: https://orcid.org/0000-0002-1403-9200)
- Shiyang Shen (ORCID: https://orcid.org/0009-0007-8895-7788)
- Yunbo Kan
- Tian Jiang (ORCID: https://orcid.org/0000-0003-0836-4303)
- Lei Zhao (ORCID: https://orcid.org/0000-0002-2253-5319)
- Minjia Tan (ORCID: https://orcid.org/0000-0002-6784-9653)
- Liming Wang (ORCID: https://orcid.org/0000-0002-9329-4559)
- Yi Li (ORCID: https://orcid.org/0000-0001-6024-9973)
- Jun Yin (ORCID: https://orcid.org/0000-0002-9453-5369)
- Tianxian Liu (ORCID: https://orcid.org/0000-0001-9368-4293)
- Mingya Zhang (ORCID: https://orcid.org/0000-0002-9712-2711)
- Yuanlin Song
- Su Feng
Institutions
- Sun Yat-sen University (CN)
- Chinese Academy of Sciences (CN)
- Fudan University (CN)
- Shanghai FRP Research Institute (China) (CN)
- Shanghai Institute of Materia Medica (CN)
- Shanghai Xuhui Central Hospital (CN)
- Zhongshan Hospital (CN)
- Inflammation Research Foundation (US)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Drug Discovery Laboratory (Norway) (NO)
- Medicina (PL)
- Baoshan University (CN)
- Shanghai Institute of Hematology (CN)
- State Key Laboratory of Drug Research
Publication Details
- Journal
- ACS Infectious Diseases
- Published
- 2025-08-12
- DOI
- https://doi.org/10.1021/acsinfecdis.4c00891
- Primary Topic
- Mycobacterium research and diagnosis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Sanofi
- Natural Science Foundation of Shanghai
- China Association for Science and Technology
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Shanghai Rising-Star Program
- Zhongshan Science and Technology Bureau
- Bethune Ethicon Excellent Surgery Foundation
- National Key Research and Development Program of China
- Program of Shanghai Academic Research Leader