TY - JOUR
T1 - Proteomic analysis of purified protein derivative of mycobacterium tuberculosis
AU - Prasad, Thottethodi Subrahmanya Keshava
AU - Verma, Renu
AU - Kumar, Satish
AU - Nirujogi, Raja Sekhar
AU - Sathe, Gajanan J.
AU - Madugundu, Anil K.
AU - Sharma, Jyoti
AU - Puttamallesh, Vinuth N.
AU - Ganjiwale, Anjali
AU - Myneedu, Vithal P.
AU - Chatterjee, Aditi
AU - Pandey, Akhilesh
AU - Harsha, H. C.
AU - Narayana, Jayasuryan
N1 - Funding Information:
Thottethodi Subrahmanya Keshava Prasad is the recipient of the DST-IDP research grant “Development of epitope based diagnostic gadget for detection of Mycobacterium tuberculosis in the Indian population” from the Department of Science Technology, Government of India. H.C. Harsha is a Wellcome Trust/DBT India Alliance Early Career Fellow. Renu Verma is a recipient of Junior Research Fellowship from University Grants Commission (UGC), Government of India. Gajanan J. Sathe is a recipient of a Junior Research Fellowship from the Council of Scientific and Industrial Research (CSIR), New Delhi, India. Anil K. Madugundu is a recipient of Junior Research Fellowship from Department of Biotechnology-Bioinformatics National Certification (DBT-BINC). Jyoti Sharma is a recipient of a Senior Research Fellowship from the CSIR, New Delhi, India. This study was supported in part by an NIH roadmap grant for Technology Centers of Networks and Pathways (U54RR020839). The data deposition to the ProteomeXchange Consortium was supported by PRIDE Team, EBI.
PY - 2013
Y1 - 2013
N2 - Background: Purified protein derivative (PPD) has been used for more than half a century as an antigen for the diagnosis of tuberculosis infection based on delayed type hypersensitivity. Although designated as "purified," in reality, the composition of PPD is highly complex and remains ill-defined. In this report, high resolution mass spectrometry was applied to understand the complexity of its constituent components. A comparative proteomic analysis of various PPD preparations and their functional characterization is likely to help in short-listing the relevant antigens required to prepare a less complex and more potent reagent for diagnostic purposes. Results: Proteomic analysis of Connaught Tuberculin 68 (PPD-CT68), a tuberculin preparation generated from M. tuberculosis, was carried out in this study. PPD-CT68 is the protein component of a commercially available tuberculin preparation, Tubersol, which is used for tuberculin skin testing. Using a high resolution LTQ-Orbitrap Velos mass spectrometer, we identified 265 different proteins. The identified proteins were compared with those identified from PPD M. bovis, PPD M. avium and PPD-S2 from previous mass spectrometry-based studies. In all, 142 proteins were found to be shared between PPD-CT68 and PPD-S2 preparations. Out of the 354 proteins from M. tuberculosis-derived PPDs (i.e. proteins in either PPD-CT68 or PPD-S2), 37 proteins were found to be shared with M. avium PPD and 80 were shared with M. bovis PPD. Alignment of PPD-CT68 proteins with proteins encoded by 24 lung infecting bacteria revealed a number of similar proteins (206 bacterial proteins shared epitopes with 47 PPD-CT68 proteins), which could potentially be involved in causing cross-reactivity. The data have been deposited to the ProteomeXchange with identifier PXD000377. Conclusions: Proteomic and bioinformatics analysis of different PPD preparations revealed commonly and differentially represented proteins. This information could help in delineating the relevant antigens represented in various PPDs, which could further lead to development of a lesser complex and better defined skin test antigen with a higher specificity and sensitivity.
AB - Background: Purified protein derivative (PPD) has been used for more than half a century as an antigen for the diagnosis of tuberculosis infection based on delayed type hypersensitivity. Although designated as "purified," in reality, the composition of PPD is highly complex and remains ill-defined. In this report, high resolution mass spectrometry was applied to understand the complexity of its constituent components. A comparative proteomic analysis of various PPD preparations and their functional characterization is likely to help in short-listing the relevant antigens required to prepare a less complex and more potent reagent for diagnostic purposes. Results: Proteomic analysis of Connaught Tuberculin 68 (PPD-CT68), a tuberculin preparation generated from M. tuberculosis, was carried out in this study. PPD-CT68 is the protein component of a commercially available tuberculin preparation, Tubersol, which is used for tuberculin skin testing. Using a high resolution LTQ-Orbitrap Velos mass spectrometer, we identified 265 different proteins. The identified proteins were compared with those identified from PPD M. bovis, PPD M. avium and PPD-S2 from previous mass spectrometry-based studies. In all, 142 proteins were found to be shared between PPD-CT68 and PPD-S2 preparations. Out of the 354 proteins from M. tuberculosis-derived PPDs (i.e. proteins in either PPD-CT68 or PPD-S2), 37 proteins were found to be shared with M. avium PPD and 80 were shared with M. bovis PPD. Alignment of PPD-CT68 proteins with proteins encoded by 24 lung infecting bacteria revealed a number of similar proteins (206 bacterial proteins shared epitopes with 47 PPD-CT68 proteins), which could potentially be involved in causing cross-reactivity. The data have been deposited to the ProteomeXchange with identifier PXD000377. Conclusions: Proteomic and bioinformatics analysis of different PPD preparations revealed commonly and differentially represented proteins. This information could help in delineating the relevant antigens represented in various PPDs, which could further lead to development of a lesser complex and better defined skin test antigen with a higher specificity and sensitivity.
KW - Biomarker
KW - Broad spectrum antibiotics
KW - Epitope
KW - Lc-ms/ms
KW - Mantoux test
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U2 - 10.1186/1559-0275-10-8
DO - 10.1186/1559-0275-10-8
M3 - Article
AN - SCOPUS:84896304657
SN - 1542-6416
VL - 10
JO - Clinical Proteomics
JF - Clinical Proteomics
IS - 1
M1 - 8
ER -