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Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB) and transmitted through inhalation of aerosolized droplets. Eighty-five percent of new TB cases occur in resource-limited countries in Asia and Africa and fewer than 40% of TB cases are diagnosed due to the lack of accurate and easy-to-...

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Autores principales: Talwar, Harvinder, Hanoudi, Samer Najeeb, Draghici, Sorin, Samavati, Lobelia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070804/
https://www.ncbi.nlm.nih.gov/pubmed/30029479
http://dx.doi.org/10.3390/v10070375
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author Talwar, Harvinder
Hanoudi, Samer Najeeb
Draghici, Sorin
Samavati, Lobelia
author_facet Talwar, Harvinder
Hanoudi, Samer Najeeb
Draghici, Sorin
Samavati, Lobelia
author_sort Talwar, Harvinder
collection PubMed
description Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB) and transmitted through inhalation of aerosolized droplets. Eighty-five percent of new TB cases occur in resource-limited countries in Asia and Africa and fewer than 40% of TB cases are diagnosed due to the lack of accurate and easy-to-use diagnostic assays. Currently, diagnosis relies on the demonstration of the bacterium in clinical specimens by serial sputum smear microscopy and culture. These methods lack sensitivity, are time consuming, expensive, and require trained personnel. An alternative approach is to develop an efficient immunoassay to detect antibodies reactive to MTB antigens in bodily fluids, such as serum. Sarcoidosis and TB have clinical and pathological similarities and sarcoidosis tissue has yielded MTB components. Using sarcoidosis tissue, we developed a T7 phage cDNA library and constructed a microarray platform. We immunoscreened our microarray platform with sera from healthy (n = 45), smear positive TB (n = 24), and sarcoidosis (n = 107) subjects. Using a student t-test, we identified 192 clones significantly differentially expressed between the three groups at a False Discovery Rate (FDR) <0.01. Among those clones, we selected the top ten most significant clones and validated them on independent test set. The area under receiver operating characteristics (ROC) for the top 10 significant clones was 1 with a sensitivity of 1 and a specificity of 1. Sequence analyses of informative phage inserts recognized as antigens by active TB sera may identify immunogenic antigens that could be used to develop therapeutic or prophylactic vaccines, as well as identify molecular targets for therapy.
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spelling pubmed-60708042018-08-09 Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection Talwar, Harvinder Hanoudi, Samer Najeeb Draghici, Sorin Samavati, Lobelia Viruses Article Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB) and transmitted through inhalation of aerosolized droplets. Eighty-five percent of new TB cases occur in resource-limited countries in Asia and Africa and fewer than 40% of TB cases are diagnosed due to the lack of accurate and easy-to-use diagnostic assays. Currently, diagnosis relies on the demonstration of the bacterium in clinical specimens by serial sputum smear microscopy and culture. These methods lack sensitivity, are time consuming, expensive, and require trained personnel. An alternative approach is to develop an efficient immunoassay to detect antibodies reactive to MTB antigens in bodily fluids, such as serum. Sarcoidosis and TB have clinical and pathological similarities and sarcoidosis tissue has yielded MTB components. Using sarcoidosis tissue, we developed a T7 phage cDNA library and constructed a microarray platform. We immunoscreened our microarray platform with sera from healthy (n = 45), smear positive TB (n = 24), and sarcoidosis (n = 107) subjects. Using a student t-test, we identified 192 clones significantly differentially expressed between the three groups at a False Discovery Rate (FDR) <0.01. Among those clones, we selected the top ten most significant clones and validated them on independent test set. The area under receiver operating characteristics (ROC) for the top 10 significant clones was 1 with a sensitivity of 1 and a specificity of 1. Sequence analyses of informative phage inserts recognized as antigens by active TB sera may identify immunogenic antigens that could be used to develop therapeutic or prophylactic vaccines, as well as identify molecular targets for therapy. MDPI 2018-07-19 /pmc/articles/PMC6070804/ /pubmed/30029479 http://dx.doi.org/10.3390/v10070375 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Talwar, Harvinder
Hanoudi, Samer Najeeb
Draghici, Sorin
Samavati, Lobelia
Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection
title Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection
title_full Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection
title_fullStr Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection
title_full_unstemmed Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection
title_short Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection
title_sort novel t7 phage display library detects classifiers for active mycobacterium tuberculosis infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070804/
https://www.ncbi.nlm.nih.gov/pubmed/30029479
http://dx.doi.org/10.3390/v10070375
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