Structure-Based Design of a B Cell Antigen from B. pseudomallei

被引:10
作者
Gaudesi, Davide [1 ]
Peri, Claudio [2 ]
Quilici, Giacomo [1 ]
Gori, Alessandro [2 ]
Ferrer-Navarro, Mario [3 ]
Conchillo-Sole, Oscar [3 ]
Thomas, Rachael [4 ]
Nithichanon, Arnone [5 ]
Lertmemongkolchai, Ganjana [5 ]
Titball, Richard [4 ]
Daura, Xavier [3 ,6 ]
Colombo, Giorgio [2 ]
Musco, Giovanna [1 ]
机构
[1] Ist Sci San Raffaele, Div Genet & Cell Biol, Biomol NMR Lab, I-20132 Milan, Italy
[2] Italian Natl Res Council, Inst Mol Recognit Chem, Dept Computat Biol, Milan, Italy
[3] Univ Autonoma Barcelona, Inst Biotechnol & Biomed, E-08193 Barcelona, Spain
[4] Univ Exeter, Coll Life & Environm Sci, Exeter, Devon, England
[5] Khon Kaen Univ, Fac Associated Med Sci, Ctr Res & Dev Med Diagnost Labs CMDL, Khon Kaen, Thailand
[6] Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain
关键词
BURKHOLDERIA-PSEUDOMALLEI; MELIOIDOSIS; VACCINE; PROTEIN; STRATEGIES; SYSTEM;
D O I
10.1021/cb500831y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Burkholderia pseudomallei is the etiological agent of melioidosis, a severe endemic disease in South-East Asia, causing septicemia and organ failure with high mortality rates. Current treatments and diagnostic approaches are largely ineffective. The development of new diagnostic tools and vaccines toward effective therapeutic opportunities against B. pseudomallei is therefore an urgent priority. In the framework of a multidisciplinary project tackling melioidosis through reverse and structural vaccinology, BPSL1050 was identified as a candidate for immunodiagnostic and vaccine development based on its reactivity against the sera of melioidosis patients. We determined its NMR solution structure and dynamics, and by novel computational methods we predicted immunogenic epitopes that once synthesized were able to elicit the production of antibodies inducing the agglutination of the bacterium and recognizing both BPSL1050 and B. pseudomallei crude extracts. Overall, these results hold promise for novel chemical biology approaches in the discovery of new diagnostic and prophylactic tools against melioidosis.
引用
收藏
页码:803 / 812
页数:10
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