title: Extensive antibody cross-reactivity among infectious gram-negative bacteria revealed by proteome microarray analysis.
abstract: Antibodies provide a sensitive indicator of proteins displayed by bacteria during sepsis. Because signals produced by infection are naturally amplified during the antibody response, host immunity can be used to identify biomarkers for proteins that are present at levels currently below detectable limits. We developed a microarray comprising approximately 70% of the 4066 proteins contained within the Yersinia pestis proteome to identify antibody biomarkers distinguishing plague from infections caused by other bacterial pathogens that may initially present similar clinical symptoms. We first examined rabbit antibodies produced against proteomes extracted from Y. pestis, Burkholderia mallei, Burkholderia cepecia, Burkholderia pseudomallei, Pseudomonas aeruginosa, Salmonella typhimurium, Shigella flexneri, and Escherichia coli, all pathogenic Gram-negative bacteria. These antibodies enabled detection of shared cross-reactive proteins, fingerprint proteins common for two or more bacteria, and signature proteins specific to each pathogen. Recognition by rabbit and non-human primate antibodies involved less than 100 of the thousands of proteins present within the Y. pestis proteome. Further antigen binding patterns were revealed that could distinguish plague from anthrax, caused by the Gram-positive bacterium Bacillus anthracis, using sera from acutely infected or convalescent primates. Thus, our results demonstrate potential biomarkers that are either specific to one strain or common to several species of pathogenic bacteria.
authors.affiliation: Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Keasey
authors.forename: Kara E
authors.initials: KE
authors.lastname: Schmid
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lee
authors.forename: James
authors.initials: J
authors.lastname: Meegan
authors.forename: Patricio
authors.initials: P
authors.lastname: Tomas
authors.forename: Michael
authors.initials: M
authors.lastname: Minto
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Tikhonov
authors.forename: Barry
authors.initials: B
authors.lastname: Schweitzer
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ulrich
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology* / Q000378:metabolism; D000917:Antibody Formation / Q000276:immunology; D001426:Bacterial Proteins / Q000378:metabolism; D003429:Cross Reactions / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology / Q000382:microbiology; D010930:Plague / Q000276:immunology; D040081:Protein Array Analysis; D011485:Protein Binding; D020543:Proteome / Q000032:analysis* / Q000276:immunology; D011817:Rabbits; D015010:Yersinia pestis / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D020543:Proteome