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Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray

BACKGROUND: Bartonella henselae is the zoonotic agent of cat scratch disease and causes potentially fatal infections in immunocompromised patients. Understanding the complex interactions between the host's immune system and bacterial pathogens is central to the field of infectious diseases and...

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Autores principales: Vigil, Adam, Ortega, Rocio, Jain, Aarti, Nakajima-Sasaki, Rie, Tan, Xiaolin, Chomel, Bruno B., Kasten, Rickie W., Koehler, Jane E., Felgner, Philip L.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897887/
https://www.ncbi.nlm.nih.gov/pubmed/20625509
http://dx.doi.org/10.1371/journal.pone.0011447
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author Vigil, Adam
Ortega, Rocio
Jain, Aarti
Nakajima-Sasaki, Rie
Tan, Xiaolin
Chomel, Bruno B.
Kasten, Rickie W.
Koehler, Jane E.
Felgner, Philip L.
author_facet Vigil, Adam
Ortega, Rocio
Jain, Aarti
Nakajima-Sasaki, Rie
Tan, Xiaolin
Chomel, Bruno B.
Kasten, Rickie W.
Koehler, Jane E.
Felgner, Philip L.
author_sort Vigil, Adam
collection PubMed
description BACKGROUND: Bartonella henselae is the zoonotic agent of cat scratch disease and causes potentially fatal infections in immunocompromised patients. Understanding the complex interactions between the host's immune system and bacterial pathogens is central to the field of infectious diseases and to the development of effective diagnostics and vaccines. METHODOLOGY: We report the development of a microarray comprised of proteins expressed from 96% (1433/1493) of the predicted ORFs encoded by the genome of the zoonotic pathogen Bartonella henselae. The array was probed with a collection of 62 uninfected, 62 infected, and 8 “specific-pathogen free” naïve cat sera, to profile the antibody repertoire elicited during natural Bartonella henselae infection. CONCLUSIONS: We found that 7.3% of the B. henselae proteins on the microarray were seroreactive and that seroreactivity was not evenly distributed between predicted protein function or subcellular localization. Membrane proteins were significantly most likely to be seroreactive, although only 23% of the membrane proteins were reactive. Conversely, we found that proteins involved in amino acid transport and metabolism were significantly underrepresented and did not contain any seroreactive antigens. Of all seroreactive antigens, 52 were differentially reactive with sera from infected cats, and 53 were equally reactive with sera from infected and uninfected cats. Thirteen of the seroreactive antigens were found to be differentially seroreactive between B. henselae type I and type II. Based on these results, we developed a classifier algorithm that was capable of accurately discerning 93% of the infected animals using the microarray platform. The seroreactivity and diagnostic potential of these antigens was then validated on an immunostrip platform, which correctly identified 98% of the infected cats. Our protein microarray platform provides a high-throughput, comprehensive analysis of the feline humoral immune response to natural infection with the alpha-proteobacterium B. henselae at an antigen-specific, sera-specific, and genome-wide level. Furthermore, these results provide novel insight and utility in diagnostics, vaccine development, and understanding of host-pathogen interaction.
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spelling pubmed-28978872010-07-12 Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray Vigil, Adam Ortega, Rocio Jain, Aarti Nakajima-Sasaki, Rie Tan, Xiaolin Chomel, Bruno B. Kasten, Rickie W. Koehler, Jane E. Felgner, Philip L. PLoS One Research Article BACKGROUND: Bartonella henselae is the zoonotic agent of cat scratch disease and causes potentially fatal infections in immunocompromised patients. Understanding the complex interactions between the host's immune system and bacterial pathogens is central to the field of infectious diseases and to the development of effective diagnostics and vaccines. METHODOLOGY: We report the development of a microarray comprised of proteins expressed from 96% (1433/1493) of the predicted ORFs encoded by the genome of the zoonotic pathogen Bartonella henselae. The array was probed with a collection of 62 uninfected, 62 infected, and 8 “specific-pathogen free” naïve cat sera, to profile the antibody repertoire elicited during natural Bartonella henselae infection. CONCLUSIONS: We found that 7.3% of the B. henselae proteins on the microarray were seroreactive and that seroreactivity was not evenly distributed between predicted protein function or subcellular localization. Membrane proteins were significantly most likely to be seroreactive, although only 23% of the membrane proteins were reactive. Conversely, we found that proteins involved in amino acid transport and metabolism were significantly underrepresented and did not contain any seroreactive antigens. Of all seroreactive antigens, 52 were differentially reactive with sera from infected cats, and 53 were equally reactive with sera from infected and uninfected cats. Thirteen of the seroreactive antigens were found to be differentially seroreactive between B. henselae type I and type II. Based on these results, we developed a classifier algorithm that was capable of accurately discerning 93% of the infected animals using the microarray platform. The seroreactivity and diagnostic potential of these antigens was then validated on an immunostrip platform, which correctly identified 98% of the infected cats. Our protein microarray platform provides a high-throughput, comprehensive analysis of the feline humoral immune response to natural infection with the alpha-proteobacterium B. henselae at an antigen-specific, sera-specific, and genome-wide level. Furthermore, these results provide novel insight and utility in diagnostics, vaccine development, and understanding of host-pathogen interaction. Public Library of Science 2010-07-06 /pmc/articles/PMC2897887/ /pubmed/20625509 http://dx.doi.org/10.1371/journal.pone.0011447 Text en Vigil 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
Vigil, Adam
Ortega, Rocio
Jain, Aarti
Nakajima-Sasaki, Rie
Tan, Xiaolin
Chomel, Bruno B.
Kasten, Rickie W.
Koehler, Jane E.
Felgner, Philip L.
Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray
title Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray
title_full Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray
title_fullStr Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray
title_full_unstemmed Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray
title_short Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray
title_sort identification of the feline humoral immune response to bartonella henselae infection by protein microarray
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897887/
https://www.ncbi.nlm.nih.gov/pubmed/20625509
http://dx.doi.org/10.1371/journal.pone.0011447
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