Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis
Introduction: The escalating global surge in Rifampicin-resistant strains poses a formidable challenge to the worldwide campaign against tuberculosis (TB), particularly in developing countries. The frequent reports of suboptimal treatment outcomes, complications, and the absence of definitive treatm...
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| Format: | Article |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1370444/full |
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| author | Yanling Wang Shijie Yin Shijie Yin Shixiong Wang Shixiong Wang Kuan Rong Xiang-He Meng Huashan Zhou Luo Jiao Da Hou Zhongjing Jiang Jun He Zenghui Mao |
| author_facet | Yanling Wang Shijie Yin Shijie Yin Shixiong Wang Shixiong Wang Kuan Rong Xiang-He Meng Huashan Zhou Luo Jiao Da Hou Zhongjing Jiang Jun He Zenghui Mao |
| author_sort | Yanling Wang |
| collection | DOAJ |
| description | Introduction: The escalating global surge in Rifampicin-resistant strains poses a formidable challenge to the worldwide campaign against tuberculosis (TB), particularly in developing countries. The frequent reports of suboptimal treatment outcomes, complications, and the absence of definitive treatment guidelines for Rifampicin-resistant spinal TB (DSTB) contribute significantly to the obstacles in its effective management. Consequently, there is an urgent need for innovative and efficacious drugs to address Rifampicin-resistant spinal tuberculosis, minimizing the duration of therapy sessions. This study aims to investigate potential targets for DSTB through comprehensive proteomic and pharmaco-transcriptomic analyses.Methods: Mass spectrometry-based proteomics analysis was employed to validate potential DSTB-related targets. PPI analysis confirmed by Immunohistochemistry (IHC) and Western blot analysis.Results: The proteomics analysis revealed 373 differentially expressed proteins (DEPs), with 137 upregulated and 236 downregulated proteins. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses delved into the DSTB-related pathways associated with these DEPs. In the context of network pharmacology analysis, five key targets—human leukocyte antigen A chain (HLAA), human leukocyte antigen C chain (HLA-C), HLA Class II Histocompatibility Antigen, DRB1 Beta Chain (HLA-DRB1), metalloproteinase 9 (MMP9), and Phospholipase C-like 1 (PLCL1)—were identified as pivotal players in pathways such as “Antigen processing and presentation” and “Phagosome,” which are crucially enriched in DSTB. Moreover, pharmaco-transcriptomic analysis can confirm that 58 drug compounds can regulate the expression of the key targets.Discussion: This research confirms the presence of protein alterations during the Rifampicin-resistant process in DSTB patients, offering novel insights into the molecular mechanisms underpinning DSTB. The findings suggest a promising avenue for the development of targeted drugs to enhance the management of Rifampicin-resistant spinal tuberculosis. |
| first_indexed | 2024-04-24T08:08:51Z |
| format | Article |
| id | doaj.art-fafb744652f6482bbd21512bab3d6896 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-24T08:08:51Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-fafb744652f6482bbd21512bab3d68962024-04-17T09:08:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-04-011510.3389/fphar.2024.13704441370444Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosisYanling Wang0Shijie Yin1Shijie Yin2Shixiong Wang3Shixiong Wang4Kuan Rong5Xiang-He Meng6Huashan Zhou7Luo Jiao8Da Hou9Zhongjing Jiang10Jun He11Zenghui Mao12Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Healthcare Affiliated to Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Healthcare Affiliated to Hunan Normal University, Changsha, ChinaCollege of Life Science, Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Healthcare Affiliated to Hunan Normal University, Changsha, ChinaCollege of Life Science, Hunan Normal University, Changsha, ChinaHunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Healthcare Affiliated to Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Healthcare Affiliated to Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Healthcare Affiliated to Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Healthcare Affiliated to Hunan Normal University, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Healthcare Affiliated to Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Healthcare Affiliated to Hunan Normal University, Changsha, ChinaIntroduction: The escalating global surge in Rifampicin-resistant strains poses a formidable challenge to the worldwide campaign against tuberculosis (TB), particularly in developing countries. The frequent reports of suboptimal treatment outcomes, complications, and the absence of definitive treatment guidelines for Rifampicin-resistant spinal TB (DSTB) contribute significantly to the obstacles in its effective management. Consequently, there is an urgent need for innovative and efficacious drugs to address Rifampicin-resistant spinal tuberculosis, minimizing the duration of therapy sessions. This study aims to investigate potential targets for DSTB through comprehensive proteomic and pharmaco-transcriptomic analyses.Methods: Mass spectrometry-based proteomics analysis was employed to validate potential DSTB-related targets. PPI analysis confirmed by Immunohistochemistry (IHC) and Western blot analysis.Results: The proteomics analysis revealed 373 differentially expressed proteins (DEPs), with 137 upregulated and 236 downregulated proteins. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses delved into the DSTB-related pathways associated with these DEPs. In the context of network pharmacology analysis, five key targets—human leukocyte antigen A chain (HLAA), human leukocyte antigen C chain (HLA-C), HLA Class II Histocompatibility Antigen, DRB1 Beta Chain (HLA-DRB1), metalloproteinase 9 (MMP9), and Phospholipase C-like 1 (PLCL1)—were identified as pivotal players in pathways such as “Antigen processing and presentation” and “Phagosome,” which are crucially enriched in DSTB. Moreover, pharmaco-transcriptomic analysis can confirm that 58 drug compounds can regulate the expression of the key targets.Discussion: This research confirms the presence of protein alterations during the Rifampicin-resistant process in DSTB patients, offering novel insights into the molecular mechanisms underpinning DSTB. The findings suggest a promising avenue for the development of targeted drugs to enhance the management of Rifampicin-resistant spinal tuberculosis.https://www.frontiersin.org/articles/10.3389/fphar.2024.1370444/fullDSTBNDSTBHLADEPsMMP9PLCL1 |
| spellingShingle | Yanling Wang Shijie Yin Shijie Yin Shixiong Wang Shixiong Wang Kuan Rong Xiang-He Meng Huashan Zhou Luo Jiao Da Hou Zhongjing Jiang Jun He Zenghui Mao Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis Frontiers in Pharmacology DSTB NDSTB HLA DEPs MMP9 PLCL1 |
| title | Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis |
| title_full | Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis |
| title_fullStr | Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis |
| title_full_unstemmed | Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis |
| title_short | Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis |
| title_sort | proteomics study the potential targets for rifampicin resistant spinal tuberculosis |
| topic | DSTB NDSTB HLA DEPs MMP9 PLCL1 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1370444/full |
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