A Burkholderia pseudomallei protein microarray reveals serodiagnostic and cross-reactive antigens.

Full Abstract

Understanding the way in which the immune system responds to infection is central to the development of vaccines and many diagnostics. To provide insight into this area, we fabricated a protein microarray containing 1,205 Burkholderia pseudomallei proteins, probed it with 88 melioidosis patient sera, and identified 170 reactive antigens. This subset of antigens was printed on a smaller array and probed with a collection of 747 individual sera derived from 10 patient groups including melioidosis patients from Northeast Thailand and Singapore, patients with different infections, healthy individuals from the USA, and from endemic and nonendemic regions of Thailand. We identified 49 antigens that are significantly more reactive in melioidosis patients than healthy people and patients with other types of bacterial infections. We also identified 59 cross-reactive antigens that are equally reactive among all groups, including healthy controls from the USA. Using these results we were able to devise a test that can classify melioidosis positive and negative individuals with sensitivity and specificity of 95% and 83%, respectively, a significant improvement over currently available diagnostic assays. Half of the reactive antigens contained a predicted signal peptide sequence and were classified as outer membrane, surface structures or secreted molecules, and an additional 20% were associated with pathogenicity, adaptation or chaperones. These results show that microarrays allow a more comprehensive analysis of the immune response on an antigen-specific, patient-specific, and population-specific basis, can identify serodiagnostic antigens, and contribute to a more detailed understanding of immunogenicity to this pathogen.

Author information

Author/s: Felgner, Philip L (PL); Kayala, Matthew A (MA); Vigil, Adam (A); Burk, Chad (C); Nakajima-Sasaki, Rie (R); Pablo, Jozelyn (J); Molina, Douglas M (DM); Hirst, Siddiqua (S); Chew, Janet S W (JS); Wang, Dongling (D); Tan, Gladys (G); Duffield, Melanie (M); Yang, Ron (R); Neel, Julien (J); Chantratita, Narisara (N); Bancroft, Greg (G); Lertmemongkolchai, Ganjana (G); Davies, D Huw (DH); Baldi, Pierre (P); Peacock, Sharon (S); Titball, Richard W (RW);

Affiliation: Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA 92697, USA. pfelgner(-atsign-)uci.edu

Grants: 5T15LM007743 (Agency:NLM NIH HHS) ; U01AI061363 (Agency:NIAID NIH HHS) ; U54065359 (Agency:PHS HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2009-Aug; vol 106 (issue 32) : pp 13499-504

Dates: Created 2009/08/26; Completed 2009/09/21;

PMID: 19666533, status: MEDLINE (last retrieval date: 9/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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