Towards Development of Improved Serodiagnostics for Tularemia by Use of Francisella tularensis Proteome Microarrays.
Tularemia in humans is caused mainly by two subspecies of the Gram-negative facultative anaerobe Francisella tularensis: F. tularensis subsp. tularensis (type A) and F. tularensis subsp. holarctica (type B). The current serological test for tularemia is based on agglutination of whole organisms, and the reactive antigens are not well understood. Previously, we profiled the antibody responses in type A and B tularemia cases in the United States using a proteome microarray of 1,741 different proteins derived from the type A strain Schu S4. Fifteen dominant antigens able to detect antibodies to both types of infection were identified, although these were not validated in a different immunoassay format. Since type A and B subspecies are closely related, we hypothesized that Schu S4 antigens would also have utility for diagnosing type B tularemia caused by strains from other geographic locations. To test this, we probed the Schu S4 array with sera from 241 type B tularemia cases in Spain. Despite there being no type A strains in Spain, we confirmed the responses against some of the same potential serodiagnostic antigens reported previously, as well as determined the responses against additional potential serodiagnostic antigens. Five potential serodiagnostic antigens were evaluated on immunostrips, and two of these (FTT1696/GroEL and FTT0975/conserved hypothetical protein) discriminated between the Spanish tularemia cases and healthy controls. We conclude that antigens from the type A strain Schu S4 are suitable for detection of antibodies from patients with type B F. tularensis infections and that these can be used for the diagnosis of tularemia in a deployable format, such as the immunostrip.
Division of Infectious Diseases, School of Medicine, University of California, Irvine, Irvine, California, USA.
Rie
R
Nakajima
Laboratorio de Espiroquetas y Patógenos Especiales, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Raquel
R
Escudero
Antigen Discovery, Inc., Irvine, California, USA.
Douglas M
DM
Molina
Laboratorio de Espiroquetas y Patógenos Especiales, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Manuela
M
Rodríguez-Vargas
Antigen Discovery, Inc., Irvine, California, USA.
Arlo
A
Randall
Division of Infectious Diseases, School of Medicine, University of California, Irvine, Irvine, California, USA.
Algis
A
Jasinskas
Antigen Discovery, Inc., Irvine, California, USA.
Jozelyn
J
Pablo
Division of Infectious Diseases, School of Medicine, University of California, Irvine, Irvine, California, USA.
Philip L
PL
Felgner
Department of Microbiology and Immunology, School of Medicine, University of Nevada, Reno, Nevada, USA.
David P
DP
AuCoin
Área de Orientación Diagnóstica, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Pedro
P
Anda
Division of Infectious Diseases, School of Medicine, University of California, Irvine, Irvine, California, USA ddavies@uci.edu.|Antigen Discovery, Inc., Irvine, California, USA.
D Huw
DH
Davies
D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000032:analysis / Q000276:immunology*; D005604:Francisella tularensis / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D046228:Microarray Analysis; D020543:Proteome / Q000032:analysis*; D012698:Serologic Tests / Q000379:methods*; D013030:Spain; D014406:Tularemia / Q000175:diagnosis*; D014481:United States
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D020543:Proteome