VIOLIN: Vaccine Investigation and Online Information Network

Burkholderia pseudomallei

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. FliC (Protective antigen)
2. LolC/E (Protective antigen)
3. PotF (Protective antigen)
Vaccine Information
References

I. General Information

1. NCBI Taxonomy ID:

28450

2. Disease:

Melioidosis

3. Introduction

The bacterium Burkholderia pseudomallei is a gram-negative saprophytic bacillus that is found predominantly in Southeast Asia and tropical Australia and is the causative agent of the emerging infection melioidosis. Infection of humans with B. pseudomallei may occur by various routes, including via wounds and existing skin lesions, aspiration of contaminated water during near-drowning, and inhalation of organisms. The clinical manifestations of melioidosis are not uniform, and patients can present with pneumonia, skin abscesses, soft tissue abscesses, or osteomyelitis/septic arthritis. Pneumonic melioidosis is presented in over 50% of acute cases of the disease, and disseminated pneumonia is associated with high mortality. Chronic melioidosis usually occurs following acute melioidosis, and relapsing melioidosis can result from the reactivation of a latent B. pseudomallei infection, often due to the withdrawal of antibiotics or the failure to complete prescribed courses of antibiotics (Harland et al., 2007).

II. Vaccine Related Pathogen Genes

1. FliC

Gene Name : FliC
VO ID : VO_0011303
NCBI Protein GI : 1929918
Other Database IDs : CDD:169576
CDD:144315
CDD:144340
Taxonomy ID : 28450
Gene Strand (Orientation) : ?
Protein Name : flagellin
Protein Length : 388
Protein Note : flagellin; Reviewed; PRK08869

Protein Sequence : Show Sequence

>gi|1929918|gb|AAB51476.1| flagellin [Burkholderia pseudomallei]
MLGINSNINSLVAQQNLNGSQGALSQAITRLSSGKRINSAADDAAGLAIATRMQTQINGLNQGVSNANDG
VSILQTASSGLTSLTNSLQRIRQLAVQASNGPLSASDASALQQEVAQQISEVNRIASQTNYNGKNILDGS
AGTLSFQVGANVGQTVSVDLTQSMSAAKIGGGMVQTGQTLGTIKVAIDSSGAAWSSGSTGQETTQINVVS
DGKGGFTFTDQNNQALSSTAVTAVFGSSTAGTGTAASPSFQTLALSTSATSALSATDQANATAMVAQINA
VNKPQTVSNLDISTQTGAYQAMVSIDNALATVNNLQATLGAAQNRFTAIATTQQAGSNNLAQAQSQIQSA
DFAQETANLSRAQVLQQAGISVLAQANSLPQQVLKLLQ

Molecule Role : Protective antigen
Molecule Role Annotation : Flagellin encoding plasmid DNA was injected into Balb/c mice intramuscularly and this elicited both a humoral and a cellular immune response. Subsequent intravenous challenge of the vaccinated Balb/c mice with 10⁵CFU of B. pseudomallei resulted in the number of bacterial cells detected in liver and/or spleen being significantly reduced in the flagellin plasmid DNA vaccinated mice. At 7 days subsequent to infection of B. pseudomallei, 5/6 (83%) of flagellin plasmid DNA vaccinated mice had survived (Chen et al., 2006).
Related Vaccine(s): B. pseudomallei DNA vaccine encoding Flagellin Protein

2. LolC/E

Gene Name : LolC/E
Sequence Strain (Speices/Organism) : Burkholderia pseudomallei K96243
VO ID : VO_0010921
NCBI Gene ID : 3093214
NCBI Protein GI : 53719887
Locus Tag : BPSL2277
Genbank Accession : BX571965
Protein Accession : YP_108873
Taxonomy ID : 272560
Chromosome No : 1
Gene Starting Position : 2742869
Gene Ending Position : 2744122
Gene Strand (Orientation) : -
Protein Name : putative lipoprotein releasing system transmembrane protein
Protein pI : 9.43
Protein Weight : 41147.07
Protein Length : 417
Protein Note : Similar to Escherichia coli lipoprotein releasing system transmembrane protein LolE SWALL:LOLE_ECOLI (SWALL:P75958) (413 aa) fasta scores: E(): 1.3e-42, 34.54% id in 414 aa, and to Ralstonia solanacearum probable lipoprotein releasing system transmembrane rsc1117 or rs05757 SWALL:Q8Y0C7 (EMBL: AL646062) (416 aa) fasta scores: E(): 1.4e-112, 71.46% id in 417 aa

DNA Sequence : Show Sequence

>gi|53717639:2742869-2744122 Burkholderia pseudomallei K96243 chromosome 1, complete sequence
GTCATTCATAGCGCAGCGCCTCCGCCGGGCGCACCTTCGCGCCGCGCCAGCTCGGATAGAGCGTCGCGAG
CGCGGACAGCGCGAAAGCGATCACGCCGATCTTGATCACGTCGCCCGCGACGAGCTCGGACGGCAGCTCG
CTGATGAAGTACACCGACGGCGGCAGGAACTGCACGCCGAACGCATGCTCGATCATCGGAATGAGCCACG
GAATGCTCCACGCGATCAGGCAGCCGAGCGCGACGCCCGTCGCGGTCCCGACGAAGCCGATCGTCACGCC
CTGCACGACGAAGATCTTCATGATCGAGCCCGGCTGCGCGCCGAGCGTGCGCAGGATCGCGATGTCCGCC
TGCTTGTTCGTCACGGTCATCACGAGCGACGACACGAGATTGAACGCCGCGACCGCGATGATCAGCGTGA
GGATGATGAACATCATCCGCTTCTCGATCTGCACCGCGGAGAACCACGTCTTGTTCTGCTGCGTCCAGTC
GCGGATGTACAGGTCGCCCGACAGCGTGTGCGCGAGCTCGCGCGCGACCTGCGGCGCCTTCTGCATGTCC
GTGAGGCGCAGCCGCACGCCCGTCGGCGCGGGCAGCCTGAAGAGCGCCTGCGCATCCTGGATGTCGATCA
TCGCAAGCGTGCTGTCGTATTCGTAGTGCCCGGACTCGAAGATGCCGACCACCGTGAACTGCTTCAGGCG
CGGCATCATCCCGGCCGGCGTGATCGTGCCTTCCGGCGCGACGAGCGTGACCTTGTCGCCGACGCCCACG
CCGAGATTGCCCGCGAGCGCGTTGCCGAGCACGATCCCGAACTGGCCGGGCGCGAGCGCGGTGAGCGCGC
CCGCCTTCATGTCCTTGCCGATGTCGGACACCTGCGGCTCGAGCGACGGCTCGACGCCGCGCAGCATCAC
GCCGCTCACCGCGTCCTGCCGCGTGAGCAGCGCCTGCGCGTCGACATACGGCGCCGCGCCGATCACCGAG
CGGTTCAGGCGCGCTTCCTTCGCGGTCAGTTGCCAGTCGGGCATCGAGCCCGTCGGCGAGAAGATCTCGA
CGTGCGCGAGCACCGACAGCATCCGGTCGCGCACCTCTTTCTGGAAGCCGTTCATCACCGACAGCACGAC
GATGAGCGCCGCGACGCCGAGCGCGATCCCGAGCATCGACACGAGCGCGATGAAGGAAATGAAGCCGTTG
CCGGTCGTGCGTTTGCCGGCGCGCGTGTAGCGCCAGCCGATCTGCCATTCGTACGGGAGTTTCA

Protein Sequence : Show Sequence

>gi|53719887|ref|YP_108873.1| putative lipoprotein releasing system transmembrane protein [Burkholderia pseudomallei K96243]
MKLPYEWQIGWRYTRAGKRTTGNGFISFIALVSMLGIALGVAALIVVLSVMNGFQKEVRDRMLSVLAHVE
IFSPTGSMPDWQLTAKEARLNRSVIGAAPYVDAQALLTRQDAVSGVMLRGVEPSLEPQVSDIGKDMKAGA
LTALAPGQFGIVLGNALAGNLGVGVGDKVTLVAPEGTITPAGMMPRLKQFTVVGIFESGHYEYDSTLAMI
DIQDAQALFRLPAPTGVRLRLTDMQKAPQVARELAHTLSGDLYIRDWTQQNKTWFSAVQIEKRMMFIILT
LIIAVAAFNLVSSLVMTVTNKQADIAILRTLGAQPGSIMKIFVVQGVTIGFVGTATGVALGCLIAWSIPW
LIPMIEHAFGVQFLPPSVYFISELPSELVAGDVIKIGVIAFALSALATLYPSWRGAKVRPAEALRYE

Molecule Role : Protective antigen
Molecule Role Annotation : LolC was evaluated as an antigen for a vaccine candidate against B. pseudomallei infection. Nonmembrane regions of the B. pseudomallei protein was expressed and purified from Escherichia coli and then evaluated as a vaccine candidate in an established mouse model of B. pseudomallei infection. When delivered with the monophosphoryl lipid A-trehalose dicorynomycolate adjuvant, the protein stimulated antigen-specific humoral and cellular immune responses. Immunization with the LolC protein domain afforded significant protection against a subsequent challenge with B. pseudomallei. LolC provided a greater level of protection when it was administered with immune-stimulating complexes complexed with CpG oligodeoxynucleotide 10103. Immunization with LolC also protected against a subsequent challenge with a heterologous strain of B. pseudomallei, demonstrating the potential utility of this protein as a vaccine antigen for melioidosis (Harland et al., 2007).
Related Vaccine(s): B. pseudomallei Subunit LolC Protein Vaccine

3. PotF

Gene Name : PotF
Sequence Strain (Speices/Organism) : Burkholderia pseudomallei K96243
VO ID : VO_0010922
NCBI Gene ID : 3095748
NCBI Protein GI : 53721504
Locus Tag : BPSS0467
Genbank Accession : BX571966
Protein Accession : YP_110489
Taxonomy ID : 272560
Chromosome No : 2
Gene Starting Position : 636534
Gene Ending Position : 637655
Gene Strand (Orientation) : -
Protein Name : putrescine ABC transport system, binding exported protein
Protein pI : 6.89
Protein Weight : 37606.43
Protein Length : 373
Protein Note : Similar to Escherichia coli putrescine-binding periplasmic protein precursor PotF or b0854 SWALL:POTF_ECOLI (SWALL:P31133) (370 aa) fasta scores: E(): 3.3e-67, 49.3% id in 357 aa, and to Pseudomonas aeruginosa polyamine transport protein pa0301 SWALL:Q9I6J0 (EMBL: AE004468) (365 aa) fasta scores: E(): 6.3e-69, 49.59% id in 367 aa. Possible alternative translational start site

DNA Sequence : Show Sequence

>gi|53721039:636534-637655 Burkholderia pseudomallei K96243 chromosome 2, complete sequence
ATCAGTGTCCCGTCTTCAATTGCGCCCACAGACGGTTCTCGAGCCGCAGGATGTCGGCGGGCATCGGCCG
CATCAGCGTCATCTTCTTGAGCACGTCCTCGGGCGGGTAGACGGTCGGGTCCTGCGCGACGGCGGGCACG
ACGAACTGTCGCGCCGCGCGGTTCGCGCTCGGGTAGAACACTTCGTTGGTGATCGCCGCGTTGACCTTCG
GGTCCTCGATGTAGTTGATCCACTTCAGCGCGGCTTCCGCGTGCGGCGCATCCTTCGGGATCACCATCAC
GTCGAACCACAGCAGGCCGCCTTCCTTCGGATTCGAGAACTTGATGTCGTACGGGCGCTTCGCCTCGGCC
GAGCGGCGATGCGCGATGCCGACGTCGCCCGACCAGCCGAGCGCGACGCATACGTCGTTGTTCGCGAGAT
CGTTGATGTAGCCGGACGAGTTGAATTGCGTGATGTACGGGCGGACTTTCTTCAGCACCTCGAACGCCGC
CTGGTAATCGGCCGGGTTCGTGCTGTTCGGATTCCTGCCCATGTATTGTAGCGTCGCGGCGAACACGTCG
ACCGCCTGATCGAGGAACGATACGCCGCAGCCCTTGAGCTTGGATACGTTCGCCGGATCGAGCACGAGCG
CCCAGCTGTCGACGGGCGCGTTCTCGCCGAGCGCCTTCTTCACCGCCTGCACGTTGTAGCCGAGGCCGTC
GGTGCCGAACGCCCACGGCACGCCGTACTGGTTGCCCGGATCGGCGTCGGCGATCATCTTCATCAGCGTC
GGATCGAGGTTCGACAGGTTCGGCAGCTTCGATTTGTCGAGCTTCTGGTAGACGCCCGCCTGAATCTGCT
TGGCCATGTAGTTCGACGTCGGCACGACGATGTCGTAGCCGGAGCTGCCCGCGAGCAGCTTCGCCTGCAG
CGTGTCGTCGCTGTCGTAGTTGTCGTACTTGACGTGGATGCCGGATTGCTTCTCGAAGTTCGGGATCGTG
TCCTTCGCGATGTAGTCCGACCAGTTGTACACGTTCAGCTCGGCGCCGGCCGCGTGCGCGGCCGGCAGGG
CGAGCGCCGACGCGCCGGCGAGCGCGACGAGCGCTGCGCGCGCGACCGCATGACGAAGATGGCTCACACT
CA

Protein Sequence : Show Sequence

>gi|53721504|ref|YP_110489.1| putrescine ABC transport system, binding exported protein [Burkholderia pseudomallei K96243]
MSVSHLRHAVARAALVALAGASALALPAAHAAGAELNVYNWSDYIAKDTIPNFEKQSGIHVKYDNYDSDD
TLQAKLLAGSSGYDIVVPTSNYMAKQIQAGVYQKLDKSKLPNLSNLDPTLMKMIADADPGNQYGVPWAFG
TDGLGYNVQAVKKALGENAPVDSWALVLDPANVSKLKGCGVSFLDQAVDVFAATLQYMGRNPNSTNPADY
QAAFEVLKKVRPYITQFNSSGYINDLANNDVCVALGWSGDVGIAHRRSAEAKRPYDIKFSNPKEGGLLWF
DVMVIPKDAPHAEAALKWINYIEDPKVNAAITNEVFYPSANRAARQFVVPAVAQDPTVYPPEDVLKKMTL
MRPMPADILRLENRLWAQLKTGH

Molecule Role : Protective antigen
Molecule Role Annotation : PotF was evaluated as an antigen for a vaccine candidate against B. pseudomallei infection. Nonmembrane regions of the B. pseudomallei protein was expressed and purified from Escherichia coli and then evaluated as a vaccine candidate in an established mouse model of B. pseudomallei infection. When delivered with the monophosphoryl lipid A-trehalose dicorynomycolate adjuvant, the protein stimulated antigen-specific humoral and cellular immune responses. Immunization with the PotF protein domain afforded significant protection against a subsequent challenge with B. pseudomallei (Harland et al., 2007).
Related Vaccine(s): B. pseudomallei Subunit PotF Protein Vaccine

III. Vaccine Information

1. B. pseudomallei DNA vaccine encoding Flagellin Protein

a. Vaccine Ontology ID:

VO_0011538

b. Type:

DNA vaccine

c. Status:

Research

d. Gene Engineering of FliC

Type: DNA vaccine construction
Description:
Detailed Gene Information: Click here.

e. Immunization Route

Intramuscular injection (i.m.)

f. Mouse Response

Host Strain: Balb/c
Vaccination Protocol: Six-week-old female Balb/c mice from groups 1–3 were injected intramuscularly (i.m.) with pcDNA3/fliC in PBS (50, 100 or 150 μg); whereas those from group 4 (the negative control) were injected (i.m) with vector DNA(150 μg; pcDNA3) in PBS, whilst those from group 5 (the positive control) were injected subcutaneously with recombinant flagellin antigens (50 μg) emulsified in complete Freund's adjuvant. Each animal from group 5 was subsequently boosted with the same dose of flagellin in incomplete Freund's adjuvant 14 days subsequent to the initial flagellin injection. The animals in groups 1–4 were boosted twice with an identical dose of plasmid DNA, once at 7 days and then again at 14 days after the initial injection (Chen et al., 2006).
Challenge Protocol: The immunized mice were infected via the tail vein with 105 CFU of mixed B. pseudomallei suspended in sterile PBS (50 μl). As control groups, the mice received either sterile PBS or vector DNA (Chen et al., 2006).
Efficacy: Subsequent intravenous challenge of the vaccinated Balb/c mice with 10(5)CFU of B. pseudomallei resulted in the number of bacterial cells detected in liver and/or spleen being significantly reduced in the flagellin plasmid DNA vaccinated mice. At 7 days subsequent to infection of B. pseudomallei, 5/6 (83%) of flagellin plasmid DNA vaccinated mice had survived (Chen et al., 2006).

2. B. pseudomallei Subunit LolC Protein Vaccine

a. Vaccine Ontology ID:

VO_0011436

b. Type:

Subunit vaccine

c. Status:

Research

d. Gene Engineering of LolC/E

Type: Recombinant protein preparation
Description:
Detailed Gene Information: Click here.

e. Immunization Route

Intraperitoneal injection (i.p.)

f. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Female 5- to 6-week-old BALB/c mice were immunized with the purified recombinant LolC protein given with adjuvant (Harland et al., 2007).
Challenge Protocol: Mice immunized with the LolC protein or appropriate controls were challenged with B. pseudomallei K96243 on day 70 (Harland et al., 2007).
Efficacy: The recombinant LolC protein afforded significant protection against the B. pseudomallei challenge (Harland et al., 2007).

3. B. pseudomallei Subunit PotF Protein Vaccine

a. Vaccine Ontology ID:

VO_0011438

b. Type:

Subunit vaccine

c. Status:

Research

d. Gene Engineering of PotF

Type: Recombinant protein preparation
Description:
Detailed Gene Information: Click here.

e. Immunization Route

Intraperitoneal injection (i.p.)

f. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Female 5- to 6-week-old BALB/c mice were immunized with the purified recombinant PotF protein given with adjuvant (Harland et al., 2007).
Challenge Protocol: Mice immunized with the PotF protein or appropriate controls were challenged with B. pseudomallei K96243 on day 70 (Harland et al., 2007).
Efficacy: Immunization with the PotF protein domain afforded significant protection against a subsequent challenge with B. pseudomallei (Harland et al., 2007).

IV. References

1. Chen et al., 2006: Chen YS, Hsiao YS, Lin HH, Yen CM, Chen SC, Chen YL. Immunogenicity and anti-Burkholderia pseudomallei activity in Balb/c mice immunized with plasmid DNA encoding flagellin. Vaccine. 2006; 24(6); 750-758. [PubMed: 16169637].

2. Harland et al., 2007: Harland DN, Chu K, Haque A, Nelson M, Walker NJ, Sarkar-Tyson M, Atkins TP, Moore B, Brown KA, Bancroft G, Titball RW, Atkins HS. Identification of a LolC homologue in Burkholderia pseudomallei, a novel protective antigen for melioidosis. Infection and immunity. 2007; 75(8); 4173-4180. [PubMed: 17517877].

3. Nelson et al., 2004: Nelson M, Prior JL, Lever MS, Jones HE, Atkins TP, Titball RW. Evaluation of lipopolysaccharide and capsular polysaccharide as subunit vaccines against experimental melioidosis. Journal of medical microbiology. 2004; 53(Pt 12); 1177-1182. [PubMed: 15585494].