Cargando…

Identification of Seroreactive Proteins of Leptospira interrogans Serovar Copenhageni Using a High-Density Protein Microarray Approach

BACKGROUND: Leptospirosis is a widespread zoonotic disease worldwide. The lack of an adequate laboratory test is a major barrier for diagnosis, especially during the early stages of illness, when antibiotic therapy is most effective. Therefore, there is a critical need for an efficient diagnostic te...

Descripción completa

Detalles Bibliográficos
Autores principales: Lessa-Aquino, Carolina, Borges Rodrigues, Camila, Pablo, Jozelyn, Sasaki, Rie, Jasinskas, Algis, Liang, Li, Wunder, Elsio A., Ribeiro, Guilherme S., Vigil, Adam, Galler, Ricardo, Molina, Douglas, Liang, Xiaowu, Reis, Mitermayer G., Ko, Albert I., Medeiros, Marco Alberto, Felgner, Philip L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798601/
https://www.ncbi.nlm.nih.gov/pubmed/24147173
http://dx.doi.org/10.1371/journal.pntd.0002499
_version_ 1782287798372401152
author Lessa-Aquino, Carolina
Borges Rodrigues, Camila
Pablo, Jozelyn
Sasaki, Rie
Jasinskas, Algis
Liang, Li
Wunder, Elsio A.
Ribeiro, Guilherme S.
Vigil, Adam
Galler, Ricardo
Molina, Douglas
Liang, Xiaowu
Reis, Mitermayer G.
Ko, Albert I.
Medeiros, Marco Alberto
Felgner, Philip L.
author_facet Lessa-Aquino, Carolina
Borges Rodrigues, Camila
Pablo, Jozelyn
Sasaki, Rie
Jasinskas, Algis
Liang, Li
Wunder, Elsio A.
Ribeiro, Guilherme S.
Vigil, Adam
Galler, Ricardo
Molina, Douglas
Liang, Xiaowu
Reis, Mitermayer G.
Ko, Albert I.
Medeiros, Marco Alberto
Felgner, Philip L.
author_sort Lessa-Aquino, Carolina
collection PubMed
description BACKGROUND: Leptospirosis is a widespread zoonotic disease worldwide. The lack of an adequate laboratory test is a major barrier for diagnosis, especially during the early stages of illness, when antibiotic therapy is most effective. Therefore, there is a critical need for an efficient diagnostic test for this life threatening disease. METHODOLOGY: In order to identify new targets that could be used as diagnostic makers for leptopirosis, we constructed a protein microarray chip comprising 61% of Leptospira interrogans proteome and investigated the IgG response from 274 individuals, including 80 acute-phase, 80 convalescent-phase patients and 114 healthy control subjects from regions with endemic, high endemic, and no endemic transmission of leptospirosis. A nitrocellulose line blot assay was performed to validate the accuracy of the protein microarray results. PRINCIPAL FINDINGS: We found 16 antigens that can discriminate between acute cases and healthy individuals from a region with high endemic transmission of leptospirosis, and 18 antigens that distinguish convalescent cases. Some of the antigens identified in this study, such as LipL32, the non-identical domains of the Lig proteins, GroEL, and Loa22 are already known to be recognized by sera from human patients, thus serving as proof-of-concept for the serodiagnostic antigen discovery approach. Several novel antigens were identified, including the hypothetical protein LIC10215 which showed good sensitivity and specificity rates for both acute- and convalescent-phase patients. CONCLUSIONS: Our study is the first large-scale evaluation of immunodominant antigens associated with naturally acquired leptospiral infection, and novel as well as known serodiagnostic leptospiral antigens that are recognized by antibodies in the sera of leptospirosis cases were identified. The novel antigens identified here may have potential use in both the development of new tests and the improvement of currently available assays for diagnosing this neglected tropical disease. Further research is needed to assess the utility of these antigens in more deployable diagnostic platforms.
format Online
Article
Text
id pubmed-3798601
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37986012013-10-21 Identification of Seroreactive Proteins of Leptospira interrogans Serovar Copenhageni Using a High-Density Protein Microarray Approach Lessa-Aquino, Carolina Borges Rodrigues, Camila Pablo, Jozelyn Sasaki, Rie Jasinskas, Algis Liang, Li Wunder, Elsio A. Ribeiro, Guilherme S. Vigil, Adam Galler, Ricardo Molina, Douglas Liang, Xiaowu Reis, Mitermayer G. Ko, Albert I. Medeiros, Marco Alberto Felgner, Philip L. PLoS Negl Trop Dis Research Article BACKGROUND: Leptospirosis is a widespread zoonotic disease worldwide. The lack of an adequate laboratory test is a major barrier for diagnosis, especially during the early stages of illness, when antibiotic therapy is most effective. Therefore, there is a critical need for an efficient diagnostic test for this life threatening disease. METHODOLOGY: In order to identify new targets that could be used as diagnostic makers for leptopirosis, we constructed a protein microarray chip comprising 61% of Leptospira interrogans proteome and investigated the IgG response from 274 individuals, including 80 acute-phase, 80 convalescent-phase patients and 114 healthy control subjects from regions with endemic, high endemic, and no endemic transmission of leptospirosis. A nitrocellulose line blot assay was performed to validate the accuracy of the protein microarray results. PRINCIPAL FINDINGS: We found 16 antigens that can discriminate between acute cases and healthy individuals from a region with high endemic transmission of leptospirosis, and 18 antigens that distinguish convalescent cases. Some of the antigens identified in this study, such as LipL32, the non-identical domains of the Lig proteins, GroEL, and Loa22 are already known to be recognized by sera from human patients, thus serving as proof-of-concept for the serodiagnostic antigen discovery approach. Several novel antigens were identified, including the hypothetical protein LIC10215 which showed good sensitivity and specificity rates for both acute- and convalescent-phase patients. CONCLUSIONS: Our study is the first large-scale evaluation of immunodominant antigens associated with naturally acquired leptospiral infection, and novel as well as known serodiagnostic leptospiral antigens that are recognized by antibodies in the sera of leptospirosis cases were identified. The novel antigens identified here may have potential use in both the development of new tests and the improvement of currently available assays for diagnosing this neglected tropical disease. Further research is needed to assess the utility of these antigens in more deployable diagnostic platforms. Public Library of Science 2013-10-17 /pmc/articles/PMC3798601/ /pubmed/24147173 http://dx.doi.org/10.1371/journal.pntd.0002499 Text en © 2013 Lessa-Aquino et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lessa-Aquino, Carolina
Borges Rodrigues, Camila
Pablo, Jozelyn
Sasaki, Rie
Jasinskas, Algis
Liang, Li
Wunder, Elsio A.
Ribeiro, Guilherme S.
Vigil, Adam
Galler, Ricardo
Molina, Douglas
Liang, Xiaowu
Reis, Mitermayer G.
Ko, Albert I.
Medeiros, Marco Alberto
Felgner, Philip L.
Identification of Seroreactive Proteins of Leptospira interrogans Serovar Copenhageni Using a High-Density Protein Microarray Approach
title Identification of Seroreactive Proteins of Leptospira interrogans Serovar Copenhageni Using a High-Density Protein Microarray Approach
title_full Identification of Seroreactive Proteins of Leptospira interrogans Serovar Copenhageni Using a High-Density Protein Microarray Approach
title_fullStr Identification of Seroreactive Proteins of Leptospira interrogans Serovar Copenhageni Using a High-Density Protein Microarray Approach
title_full_unstemmed Identification of Seroreactive Proteins of Leptospira interrogans Serovar Copenhageni Using a High-Density Protein Microarray Approach
title_short Identification of Seroreactive Proteins of Leptospira interrogans Serovar Copenhageni Using a High-Density Protein Microarray Approach
title_sort identification of seroreactive proteins of leptospira interrogans serovar copenhageni using a high-density protein microarray approach
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798601/
https://www.ncbi.nlm.nih.gov/pubmed/24147173
http://dx.doi.org/10.1371/journal.pntd.0002499
work_keys_str_mv AT lessaaquinocarolina identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT borgesrodriguescamila identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT pablojozelyn identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT sasakirie identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT jasinskasalgis identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT liangli identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT wunderelsioa identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT ribeiroguilhermes identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT vigiladam identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT gallerricardo identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT molinadouglas identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT liangxiaowu identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT reismitermayerg identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT koalberti identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT medeirosmarcoalberto identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach
AT felgnerphilipl identificationofseroreactiveproteinsofleptospirainterrogansserovarcopenhageniusingahighdensityproteinmicroarrayapproach