Quantitative proteomics reveals that dormancy-related proteins mediate the attenuation in mycobacterium strains

Virulence

Shujia Wu¹  Liqun Zhang²  Jinshuai Sun³  Hong Wang⁴  Erhei Dai⁵  Jiaqi Yang⁵  Haican Liu⁶  Kanglin Wan⁶  Xiuqin Zhao⁶  Li Wan⁷  Tao Zhang⁸  Yao Zhang⁸  Lei Chang⁸  Huiming Zhu⁹  Songhao Jiang^1,10  Shuhong Meng^1,10  Jiahui Shi^1,10  Ping Xu^1,11 

[1] Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, Chin;Department of Tuberculosis, Capital Medical University, Beijing Chest Hospital, Beijing, Chin;Key Laboratory of Microbial Diversity Research and Application of Hebei Province, School of Life Sciences, Hebei University, Hebei, Chin;School of Public Health, North China University of Science and Technology, Tangshan, Chin;State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing, Chin;The Fifth Hospital of Shijiazhuang, School of Public Health, North China University of Science and Technology, Shijiazhuang, Chin;School of Public Health, North China University of Science and Technology, Tangshan, Chin;The Fifth Hospital of Shijiazhuang, School of Public Health, North China University of Science and Technology, Shijiazhuang, Chin;State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, Chin;State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, Chin;The Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, Chin;State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing, Chin;State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing, Chin;Department of Biomedicine, School of Medicine, Guizhou University, Guiyang, Chin;State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing, Chin;Key Laboratory of Microbial Diversity Research and Application of Hebei Province, School of Life Sciences, Hebei University, Hebei, Chin;State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing, Chin;Key Laboratory of Microbial Diversity Research and Application of Hebei Province, School of Life Sciences, Hebei University, Hebei, Chin;Department of Biomedicine, School of Medicine, Guizhou University, Guiyang, Chin;Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, Chin;

关键词: Mycobacterium tuberculosis;    quantitative proteomics;    virulence;    attenuation;    dormancy;   

DOI  :  10.1080/21505594.2021.1965703

来源: Taylor & Francis

【 摘 要 】

Although members of the Mycobacterium tuberculosis complex (MTBC) exhibit high similarity, they are characterized by differences with respect to virulence, immune response, and transmissibility. To understand the virulence of these bacteria and identify potential novel therapeutic targets, we systemically investigated the total cell protein contents of virulent H37Rv, attenuated H37Ra, and avirulent M. bovis BCG vaccine strains at the log and stationary phases, based on tandem mass tag (TMT) quantitative proteomics. Data analysis revealed that we obtained deep-coverage protein identification and high quantification. Although 272 genetic variations were reported in H37Ra and H37Rv, they showed very little expression difference in log and stationary phase. Quantitative comparison revealed H37Ra and H37Rv had significantly dysregulation in log phase (227) compared with stationary phase (61). While BCG and H37Rv, and BCG and H37Ra showed notable differences in stationary phase (1171 and 1124) with respect to log phase (381 and 414). In the log phase, similar patterns of protein abundance were observed between H37Ra and BCG, whereas a more similar expression pattern was observed between H37Rv and H37Ra in the stationary phase. Bioinformatic analysis revealed that the upregulated proteins detected for H37Rv and H37Ra in log phase were virulence-related factors. In both log and stationary phases, the dysregulated proteins detected for BCG, which have also been identified as M. tuberculosis response proteins under dormancy conditions. We accordingly describe the proteomic profiles of H37Rv, H37Ra, and BCG, which we believe will potentially provide a better understanding of H37Rv pathogenesis, H37Ra attenuation, and BCG immuno protection.

【 授权许可】

CC BY