Proteomic profiling of peripheral blood mononuclear cells isolated from patients with tuberculosis and diabetes copathogenesis - A pilot study

Background Diabetes is an important risk factor for developing tuberculosis. This association leads to exacerbation of tuberculosis symptoms and delayed treatment of both the diseases. Molecular mechanism and biomarkers/drug targets related to copathogenesis of tuberculosis and diabetes, however, still remains to be poorly understood. In this study, proteomics based 2D-MALDI/MS approach was employed to identify host signature proteins which are altered during copathogenesis of tuberculosis and diabetes. Methods Comparative proteome of human peripheral blood mononuclear cells (PBMCs) from healthy controls, tuberculosis and diabetes patients in comparison to comorbid diabetes and tuberculosis patients was analyzed. Gel based proteomics approach followed by in gel trypsin digestion and peptide identification by mass spectrometry was used for signature protein identification. Results Total of 18 protein spots with differential expression in TBDM patients in comparison to other groups were identified. These include Vimentin, tubulin beta chain protein, superoxide dismutase, Actin related protein 2/3 complex subunit 2, PDZ LIM domain protein, Rho-GDP dissociation inhibitor, Ras related protein Rab, dCTPpyrophosphatase 1, Transcription initiation factor TFIID subunit 12, coffilin 1, three isoforms of Peptidylprolylcis-trans isomerase A, three isoforms of Protein S100A9, Protein S100A8 and SH3 domain containing protein. These proteins belonged to four functional categories i.e. structural, cell cycle/growth regulation, signaling and intermediary metabolism. Conclusion Proteins identified to be differentially expressed in TBDM patient can act as potent biomarkers and as predictors for copathogenesis of tuberculosis and diabetes.

[1]  M. I. Sari,et al.  Superoxide Dismutase Levels and Polymorphism (Ala16val) In Tuberculosis Patients with Diabetes Mellitus in Medan City , 2019, Open access Macedonian journal of medical sciences.

[2]  Jianhong Wu,et al.  The mechanism of cytoskeleton protein β-actin and cofilin-1 of macrophages infected by Mycobacterium avium. , 2016, American journal of translational research.

[3]  T. Kaisho,et al.  PDLIM1 inhibits NF-κB-mediated inflammatory signaling by sequestering the p65 subunit of NF-κB in the cytoplasm , 2015, Scientific Reports.

[4]  M. Ezzati,et al.  Effect of diabetes on tuberculosis control in 13 countries with high tuberculosis: a modelling study. , 2015, The lancet. Diabetes & endocrinology.

[5]  U. Schaible,et al.  Macrophage defense mechanisms against intracellular bacteria , 2015, Immunological reviews.

[6]  Jicheng Li,et al.  Serum protein S100A9, SOD3, and MMP9 as new diagnostic biomarkers for pulmonary tuberculosis by iTRAQ‐coupled two‐dimensional LC‐MS/MS , 2015, Proteomics.

[7]  G. MacBeath,et al.  Systematic Analysis of Bacterial Effector-Postsynaptic Density 95/Disc Large/Zonula Occludens-1 (PDZ) Domain Interactions Demonstrates Shigella OspE Protein Promotes Protein Kinase C Activation via PDLIM Proteins* , 2014, The Journal of Biological Chemistry.

[8]  A. Geffken,et al.  WASH‐driven actin polymerization is required for efficient mycobacterial phagosome maturation arrest , 2014, Cellular microbiology.

[9]  J. Nielsen,et al.  Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics. , 2014, Molecular & cellular proteomics : MCP.

[10]  M. Selman,et al.  S100A8/A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis. , 2013, American journal of respiratory and critical care medicine.

[11]  F. Shao,et al.  Structurally Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to Counteract Host Defenses , 2012, Cell.

[12]  Y. Koide,et al.  Rab GTPases Regulating Phagosome Maturation Are Differentially Recruited to Mycobacterial Phagosomes , 2011, Traffic.

[13]  R. Angeletti,et al.  Proteomic analysis of endocytic vesicles: Rab1a regulates motility of early endocytic vesicles , 2011, Journal of Cell Science.

[14]  K. Adipietro,et al.  Rab1 small GTP-binding protein regulates cell surface trafficking of the human calcium-sensing receptor. , 2010, Endocrinology.

[15]  Reuben Granich,et al.  HIV infection-associated tuberculosis: the epidemiology and the response. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  C. Snehalatha,et al.  Diabetes in Asia , 2010, The Lancet.

[17]  R. Gie,et al.  High prevalence of Mycobacterium tuberculosis infection and disease in children and adolescents with type 1 diabetes mellitus. , 2009, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[18]  B. Restrepo Convergence of the tuberculosis and diabetes epidemics: renewal of old acquaintances. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  D. Foell,et al.  Mechanisms of Disease: a 'DAMP' view of inflammatory arthritis , 2007, Nature Clinical Practice Rheumatology.

[20]  Johanna Ivaska,et al.  Novel functions of vimentin in cell adhesion, migration, and signaling. , 2007, Experimental cell research.

[21]  N. Rawal,et al.  Vimentin Expressed on Mycobacterium tuberculosis-Infected Human Monocytes Is Involved in Binding to the NKp46 Receptor1 , 2006, The Journal of Immunology.

[22]  B. Alisjahbana,et al.  Exposure to rifampicin is strongly reduced in patients with tuberculosis and type 2 diabetes. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  N. Balde,et al.  Associated tuberculosis and diabetes in Conakry, Guinea: prevalence and clinical characteristics. , 2006, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[24]  M. Ansari,et al.  COMPARISON OF LEVELS OF NITRIC OXIDE, SUPEROXIDE DISMUTASE AND GLUTATHIONE PEROXIDASE OF GASTRIC JUICE IN INFECTED AND NON-INFECTED PATIENTS WITH HELICOBACTER PYLORI , 2006 .

[25]  P. Rouleau,et al.  Proinflammatory Activities of S100: Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion 1 , 2003, The Journal of Immunology.

[26]  S. Narumiya,et al.  Rho-associated Kinase ROCK Activates LIM-kinase 1 by Phosphorylation at Threonine 508 within the Activation Loop* , 2000, The Journal of Biological Chemistry.

[27]  G. Aderaye,et al.  Prevalence and clinical features of tuberculosis in Ethiopian diabetic patients. , 1999, East African medical journal.

[28]  R. Miller,et al.  HIV associated tuberculosis , 1997, BMJ.

[29]  M. Schreier,et al.  Molecular Mechanisms of Immunosuppression by Cyclosporins , 1993, Annals of the New York Academy of Sciences.

[30]  H. Nakata,et al.  [Serum superoxide dismutase (SOD) activity in diabetes mellitus]. , 1993, Rinsho byori. The Japanese journal of clinical pathology.

[31]  A. Cerami,et al.  Identification of cyclophilin as a proinflammatory secretory product of lipopolysaccharide-activated macrophages. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[32]  N. Hogg,et al.  Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. , 1991, The Journal of biological chemistry.

[33]  T. Hayano,et al.  Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin , 1989, Nature.

[34]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[35]  Y. Xu,et al.  [Rearrangement and altered expression of actin in macrophages induced by Mycobacterium tuberculosis]. , 2003, Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases.

[36]  World Health Organization, , 2003 .

[37]  S. Ramachandran,et al.  O R I G I N a L I N V E S T I G a T I O N Open Access Cardio Vascular Diabetology Introduction , 2022 .