Abstract
Burkholderia pseudomallei is a Gram-negative bacterium responsible for melioidosis, a serious and often fatal infectious disease that is poorly controlled by existing treatments. Due to its inherent resistance to the major antibiotic classes and its facultative intracellular pathogenicity, an effective vaccine would be extremely desirable, along with appropriate prevention and therapeutic management. One of the main subunit vaccine candidates is flagellin of Burkholderia pseudomallei (FliCBp). Here, we present the high resolution crystal structure of FliCBp and report the synthesis and characterization of three peptides predicted to be both B and T cell FliCBp epitopes, by both structure-based in silico methods, and sequence-based epitope prediction tools. All three epitopes were shown to be immunoreactive against human IgG antibodies and to elicit cytokine production from human peripheral blood mononuclear cells. Furthermore, two of the peptides (F51-69 and F270-288) were found to be dominant immunoreactive epitopes, and their antibodies enhanced the bactericidal activities of purified human neutrophils. The epitopes derived from this study may represent potential melioidosis vaccine components.
Highlights
Burkholderia pseudomallei, a pathogenic Gram-negative bacterium present in soil and water, is responsible for melioidosis, an often fatal infectious disease that is most frequently reported in tropical regions of the world, especially in Thailand and northern Australia, where the disease is endemic [1]
F51-69 overlaps with Peptide 6; F96-111 overlaps with Peptide 10, and F270-288 overlaps with Peptide 28 from the peptide panel synthesized by Musson et al The following peptides were synthesized as described in the Materials and Methods section: F51-69; 51-TRMQTQINGLNQGVSNAND-69, F96-111; 96-VQASNGPLSASDASAL-111, F270-288; 270-NATAMVAQINAVNKPQTVS-288
Predicted FliCBp epitope peptides, F51-69 and F270-288 are recognized by human antibodies (IgG) in serum, and elicit responses from human peripheral blood mononuclear cell (PBMC)
Summary
Burkholderia pseudomallei, a pathogenic Gram-negative bacterium present in soil and water, is responsible for melioidosis, an often fatal infectious disease that is most frequently reported in tropical regions of the world, especially in Thailand and northern Australia, where the disease is endemic [1]. Diagnosis and treatment of melioidosis are far from adequate, as symptoms lack a specific signature necessary for rapid diagnosis, and the bacterium is inherently resistant to many commercially available classes of antibiotics. Over the last few years, the study of melioidosis has become increasingly relevant, as a public health concern, and due to bioterrorism implications, since B. pseudomallei is classified as a category B infective agent. The use of attenuated forms of B. pseudomallei presents significant safety issues due to its capacity to remain dormant and cause infections years later, it is clear that alternative approaches must be sought
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