|
Klebsiella pneumoniae |
Table of Contents |
- General Information
- NCBI Taxonomy ID
- Disease
- Introduction
- Vaccine Related Pathogen Genes
- fyuA
(Protective antigen)
- Vaccine Information
- c-di-GMP [c- diguanylate]
- Capsular types Kl, K36, K44 and K Cross
- CpG ODN (Two CpG motifs)
- CPS2 (Capsule polysaccharide)
- CRM197-1 (Synthetic hexasaccharide)
- K. pneumoniae polysaccharide-tetanus toxoid conjugate vaccine
- Klebesiella FuyA protein vaccine
- References
|
I. General Information |
1. NCBI Taxonomy ID: |
573 |
2. Disease: |
Pneumonia, Bloodstream infections, Abscess |
3. Introduction |
Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It can cause different types of healthcare-associated infections, including pneumonia, bloodstream infections, abscesses, and meningitis. The genus Klebsiella was named after the German microbiologist Edwin Klebs (1834–1913). Klebsiella pneumoniae naturally occurs in the soil, and about 30% of strains can fix nitrogen in anaerobic conditions. It can also be found in the normal flora of the mouth, skin, and intestines. However, if aspirated, It can cause destructive changes to human and animal lungs, specifically to the alveoli resulting in bloody, brownish or yellow colored jelly-like sputum. |
II. Vaccine Related Pathogen Genes |
1. fyuA |
-
Gene Name :
fyuA
-
NCBI Protein GI :
WP_142468275
-
Other Database IDs :
CDD:273805
CDD:238657
-
Taxonomy ID :
570
-
Gene Strand (Orientation) :
?
-
Protein Name :
siderophore yersiniabactin receptor FyuA
-
Protein pI :
5.38
-
Protein Weight :
71520.78
-
Protein Length :
768
-
Protein Note :
TonB-dependent siderophore receptor; TIGR01783
-
Protein Sequence : Show Sequence
>WP_142468275.1 MULTISPECIES: siderophore yersiniabactin receptor FyuA [Klebsiella]
MKMTRFYPLVLGGFLLPAAAHSQTSQQDESTLVVTASKQSSHSASANNVSSTVISATELSDAGVTASDKL
PRVLPGLNIENSGNMLFSTISLRGISSAQDFYNPAVTLYVDGVPQLSTNTIQALTDVQSVELLRGPQGTL
YGKSAQGGIINIVTQQPDSTPRGYIEGGVSSRDSYRSKLNLSGPIQDGLLYGSVTLLRQVDDGEMINPST
GSDDLGGTRASIGNVKLRLAPDDQPWEMGFSASRECTRATQDAYVAWNDLKSRTLSLSEGSPDPYLRRCT
DSQTLSGKYATDDWVFNLIGAWQQQNYSRTFPSGSLIVNMPQRWNQDVQELRAATLGDTRTVDMVFGLYR
QNTREKLNSAYDMPTMPYLSSTGYTTAETLAAYSDLTWHLTERFDIGGGVRFSHDKASTQYHGSMLGNPF
GDQGKSNDDRVLGQLSAGYLLTDDWRVYTRVAQGYKPSGYNIVPTAGLDAKPFNAEKSINYEIGTRYETA
DVTLQAATFYTHTKDMQLYSGPVGMQTLSNAGRANATGVELEAKWRFAQGWSWDINGNMIHSEFTNDSEL
YHGNRVPFVPRYGAGSSVNGVIDTRYGALMPRLAVNLVGPHYFDGDNQLRQGTYATLDSSIGWQATERMN
ISVYVDNLFDRRYRTYGYMNGSSAVAQVNMGRTVGINTRIDFF
-
Molecule Role :
Protective antigen
- Related Vaccine(s):
Klebesiella FuyA protein vaccine
|
III. Vaccine Information |
![](../images/ul.gif) |
|
![](../images/ur.gif) |
|
|
|
1. c-di-GMP [c- diguanylate] |
a. Type: |
Subunit vaccine |
b. Status: |
Research |
c. Host Species for Licensed Use: |
Mouse |
d. Antigen |
The c-di-GMP used in these studies was chemically synthesized and prepared (Karaolis et al., 2007) |
e. Preparation |
The c-di-GMP used in these studies was chemically synthesized and prepared (Karaolis et al., 2007) |
f. Immunization Route |
i.t. |
|
|
|
![](../images/ll.gif) |
|
![](../images/lr.gif) |
|
|
![](../images/ul.gif) |
|
![](../images/ur.gif) |
|
|
|
2. Capsular types Kl, K36, K44 and K Cross |
a. Type: |
Subunit vaccine |
b. Status: |
Research |
c. Host Species for Licensed Use: |
Mouse |
d. Antigen |
Capsular types Kl, K36, K44 and K Cross (Roe and Jones, 1984) |
e. Preparation |
Capsular were extracted from culture filtrates of K. aerogenes Kl a, Kl b, Kl c,K36, K44 and K Cross. |
f. Immunization Route |
Intraperitoneal injection (i.p.) |
|
|
|
![](../images/ll.gif) |
|
![](../images/lr.gif) |
|
|
![](../images/ul.gif) |
|
![](../images/ur.gif) |
|
|
|
3. CpG ODN (Two CpG motifs) |
a. Type: |
Subunit vaccine |
b. Status: |
Research |
c. Host Species for Licensed Use: |
Mouse |
d. Antigen |
Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotide motifs (CpG ODN) (Deng et al., 2004) |
e. Preparation |
Active and control CpG ODN were synthesized on a phosphodiester backbone by Oligos Etc. (Deng et al., 2004) |
f. Immunization Route |
i.t. |
|
|
|
![](../images/ll.gif) |
|
![](../images/lr.gif) |
|
|
![](../images/ul.gif) |
|
![](../images/ur.gif) |
|
|
|
4. CPS2 (Capsule polysaccharide) |
a. Type: |
Subunit vaccine |
b. Status: |
Research |
c. Host Species for Licensed Use: |
Macaque |
d. Antigen |
ST258 capsule polysaccharide type 2(CPS2) (Malachowa et al., 2019) |
e. Preparation |
CPS2 was extracted from K. pneumoniae NJST258_2 culture supernatant (Malachowa et al., 2019) |
f. Immunization Route |
Intramuscular injection (i.m.) |
|
|
|
![](../images/ll.gif) |
|
![](../images/lr.gif) |
|
|
![](../images/ul.gif) |
|
![](../images/ur.gif) |
|
|
|
5. CRM197-1 (Synthetic hexasaccharide) |
a. Type: |
Conjugate vaccine |
b. Status: |
Research |
c. Host Species for Licensed Use: |
Mouse |
d. Antigen |
CRM197-1 (Synthetic hexasaccharide) (Seeberger et al., 2017) |
e. Preparation |
the convergent [3+3] synthesis of the hexasaccharide repeating unit from its capsular polysaccharide and related sequences (Seeberger et al., 2017) |
f. Immunization Route |
subcutaneous injection |
|
|
|
![](../images/ll.gif) |
|
![](../images/lr.gif) |
|
|
![](../images/ul.gif) |
|
![](../images/ur.gif) |
|
|
|
6. K. pneumoniae polysaccharide-tetanus toxoid conjugate vaccine |
a. Type: |
Conjugate vaccine |
b. Status: |
Research |
c. Host Species for Licensed Use: |
Rat |
d. Antigen |
The polysaccharide (PS) derived from K. pneumoniae NCTC 5055 lipopolysaccharide (LPS) (Chhibber et al., 2005) |
e. Preparation |
The polysaccharide (PS) derived from K. pneumoniae NCTC 5055 lipopolysaccharide (LPS) was covalently linked to tetanus toxoid by using carbodimide with adipic acid dihydrazide as a spacer molecule (Chhibber et al., 2005). |
f. Immunization Route |
Intramuscular injection (i.m.) |
|
|
|
![](../images/ll.gif) |
|
![](../images/lr.gif) |
|
|
![](../images/ul.gif) |
|
![](../images/ur.gif) |
|
|
|
7. Klebesiella FuyA protein vaccine |
a. Type: |
Subunit vaccine |
b. Status: |
Research |
c. Host Species for Licensed Use: |
Mouse |
d. Antigen |
FuyA (Yersinia bactin receptor FyuA) (Kumar et al., 2020) |
e. Gene Engineering of
fyuA |
- Type:
Recombinant protein preparation
- Description:
Yersiniabactin receptor coding gene FyuA of Klebsiella pneumoniae ATCC 43816 was amplified by colony PCR using the primers Forward 5′- AAGGATCCATGAAAATGACACGGCTTTAT-3'and Reverse5′- AACTCGAGTCAGAAGAAATCAATTCGCGT-3′ which were designed for the sequence with accession id NC_012731.1. The restriction sites BamHI and XhoI were present in forward and reverse primers respectively to generate sticky ends for cloning into the vector. The amplified gene was cloned into pET28a to produce N-terminally tagged hexahistidine fusions. The resulting constructs were verified by sequencing. The constructs without mutations were transformed into E.coli BL21 expression host. The expression was induced by the addition of 1 mM IPTG and further incubation at 37 °C with aeration for 4 h before harvesting the cells by centrifugation (Kumar et al., 2020).
- Detailed Gene Information: Click here.
|
f. Vector: |
pET28a |
g. Allergen: |
FuyA (Yersinia bactin receptor FyuA) |
h. Preparation |
Yersiniabactin receptor coding gene FyuA of Klebsiella pneumoniae ,ATCC 43816 was amplified by colony PCR.The amplified gene was cloned into pET28a to produce N-terminally tagged hexahistidine fusions (Kumar et al., 2020) |
i. Immunization Route |
intranasal immunization |
|
|
|
![](../images/ll.gif) |
|
![](../images/lr.gif) |
|
|
IV. References |
1. Ahmad et al., 2012: Ahmad TA, Haroun M, Hussein AA, El Ashry el SH, El-Sayed LH. Development of a new trend conjugate vaccine for the prevention of Klebsiella pneumoniae. Infectious disease reports. 2012; 4(2); e33. [PubMed: 24470947].
2. Babu et al., 2017: Babu L, Uppalapati SR, Sripathy MH, Reddy PN. Evaluation of Recombinant Multi-Epitope Outer Membrane Protein-Based Klebsiella pneumoniae Subunit Vaccine in Mouse Model. Frontiers in microbiology. 2017; 8; 1805. [PubMed: 28979250].
3. Chathley et al., 1996: Chathley UC, Sharma S, Chhibber S. Lipopolysaccharide-induced resistance in mice against ascending urinary tract infection with Klebsiella pneumoniae. Folia microbiologica. 1996; 41(4); 373-376. [PubMed: 9131794].
4. Chhibber and Bajaj, 1995: Chhibber S, Bajaj J. Polysaccharide-iron-regulated cell surface protein conjugate vaccine: its role in protection against Klebsiella pneumoniae-induced lobar pneumonia. Vaccine. 1995; 13(2); 179-184. [PubMed: 7625113].
5. Chhibber et al., 2005: Chhibber S, Rani M, Vanashree Y. Immunoprotective potential of polysaccharide-tetanus toxoid conjugate in Klebsiella pneumoniae induced lobar pneumonia in rats. Indian journal of experimental biology. 2005; 43(1); 40-45. [PubMed: 15691064].
6. Clements et al., 2008: Clements A, Jenney AW, Farn JL, Brown LE, Deliyannis G, Hartland EL, Pearse MJ, Maloney MB, Wesselingh SL, Wijburg OL, Strugnell RA. Targeting subcapsular antigens for prevention of Klebsiella pneumoniae infections. Vaccine. 2008; 26(44); 5649-5653. [PubMed: 18725260].
7. Cooper and Rowley, 1982: Cooper JM, Rowley D. Resistance to Klebsiella pneumoniae and the importance of two bacterial antigens. The Australian journal of experimental biology and medical science. 1982; 60(6); 629-641. [PubMed: 6820634].
8. Cryz et al., 1984: Cryz SJ Jr, Fürer E, Germanier R. Protection against fatal Klebsiella pneumoniae burn wound sepsis by passive transfer of anticapsular polysaccharide. Infection and immunity. 1984; 45(1); 139-142. [PubMed: 6376353].
9. Cryz et al., 1986: Cryz SJ Jr, Fürer E, Germanier R. Immunization against fatal experimental Klebsiella pneumoniae pneumonia. Infection and immunity. 1986; 54(2); 403-407. [PubMed: 3533779].
10. Deng et al., 2004: Deng JC, Moore TA, Newstead MW, Zeng X, Krieg AM, Standiford TJ. CpG oligodeoxynucleotides stimulate protective innate immunity against pulmonary Klebsiella infection. Journal of immunology (Baltimore, Md. : 1950). 2004; 173(8); 5148-5155. [PubMed: 15470059].
11. Feldman et al., 2019: Feldman MF, Mayer Bridwell AE, Scott NE, Vinogradov E, McKee SR, Chavez SM, Twentyman J, Stallings CL, Rosen DA, Harding CM. A promising bioconjugate vaccine against hypervirulent Klebsiella pneumoniae. Proceedings of the National Academy of Sciences of the United States of America. 2019; 116(37); 18655-18663. [PubMed: 31455739].
12. Hegerle et al., 2018: Hegerle N, Choi M, Sinclair J, Amin MN, Ollivault-Shiflett M, Curtis B, Laufer RS, Shridhar S, Brammer J, Toapanta FR, Holder IA, Pasetti MF, Lees A, Tennant SM, Cross AS, Simon R. Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa. PloS one. 2018; 13(9); e0203143. [PubMed: 30188914].
13. Hsieh et al., 2013: Hsieh PF, Liu JY, Pan YJ, Wu MC, Lin TL, Huang YT, Wang JT. Klebsiella pneumoniae peptidoglycan-associated lipoprotein and murein lipoprotein contribute to serum resistance, antiphagocytosis, and proinflammatory cytokine stimulation. The Journal of infectious diseases. 2013; 208(10); 1580-1589. [PubMed: 23911714].
14. Hussein et al., 2018: Hussein KE, Bahey-El-Din M, Sheweita SA. Immunization with the outer membrane proteins OmpK17 and OmpK36 elicits protection against Klebsiella pneumoniae in the murine infection model. Microbial pathogenesis. 2018; 119; 12-18. [PubMed: 29626658].
15. Jain et al., 2015: Jain RR, Mehta MR, Bannalikar AR, Menon MD. Alginate microparticles loaded with lipopolysaccharide subunit antigen for mucosal vaccination against Klebsiella pneumoniae. Biologicals : journal of the International Association of Biological Standardization. 2015; 43(3); 195-201. [PubMed: 25737397].
16. Karaolis et al., 2007: Karaolis DK, Newstead MW, Zeng X, Hyodo M, Hayakawa Y, Bhan U, Liang H, Standiford TJ. Cyclic di-GMP stimulates protective innate immunity in bacterial pneumonia. Infection and immunity. 2007; 75(10); 4942-4950. [PubMed: 17646358].
17. Kuenen et al., 1994: Kuenen JD, van Dijke EE, Hol C, Bootsma HJ, Verhoef J, van Dijk H. Protective effects of orally administered, Klebsiella-containing bacterial lysates in mice. FEMS immunology and medical microbiology. 1994; 8(1); 69-75. [PubMed: 8156053].
18. Kumar et al., 2020: Kumar A, Harjai K, Chhibber S. Early cytokine response to lethal challenge of Klebsiella pneumoniae averted the prognosis of pneumonia in FyuA immunized mice. Microbial pathogenesis. 2020; 144; 104161. [PubMed: 32194179].
19. Kurupati et al., 2011: Kurupati P, Ramachandran NP, Poh CL. Protective efficacy of DNA vaccines encoding outer membrane protein A and OmpK36 of Klebsiella pneumoniae in mice. Clinical and vaccine immunology : CVI. 2011; 18(1); 82-88. [PubMed: 21048001].
20. Lavender et al., 2005: Lavender H, Jagnow JJ, Clegg S. Klebsiella pneumoniae type 3 fimbria-mediated immunity to infection in the murine model of respiratory disease. International journal of medical microbiology : IJMM. 2005; 295(3); 153-159. [PubMed: 16047414].
21. Lee et al., 2015: Lee WH, Choi HI, Hong SW, Kim KS, Gho YS, Jeon SG. Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity. Experimental & molecular medicine. 2015; 47(9); e183. [PubMed: 26358222].
22. Malachowa et al., 2019: Malachowa N, Kobayashi SD, Porter AR, Freedman B, Hanley PW, Lovaglio J, Saturday GA, Gardner DJ, Scott DP, Griffin A, Cordova K, Long D, Rosenke R, Sturdevant DE, Bruno D, Martens C, Kreiswirth BN, DeLeo FR. Vaccine Protection against Multidrug-Resistant Klebsiella pneumoniae in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection. mBio. 2019; 10(6); . [PubMed: 31848292].
23. Nimier et al., 1999: Nimier K, Wolff F, Allouch PY, Guy-Grand D, Bloy C. Protective effects of RU 41740, a bacterial immunomodulator, against experimental infections: induction of cytokine and immunoglobulin release in mice after oral administration. International journal of immunopharmacology. 1999; 21(9); 561-574. [PubMed: 10501625].
24. Peng et al., 2021: Peng Z, Wu J, Wang K, Li X, Sun P, Zhang L, Huang J, Liu Y, Hua X, Yu Y, Pan C, Wang H, Zhu L. Production of a Promising Biosynthetic Self-Assembled Nanoconjugate Vaccine against Klebsiella Pneumoniae Serotype O2 in a General Escherichia Coli Host. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2021; 8(14); e2100549. [PubMed: 34032027].
25. Rani et al., 1990: Rani M, Gupta RK, Chhibber S. Protection against Klebsiella pneumoniae induced lobar pneumonia in rats with lipopolysaccharide and related antigens. Canadian journal of microbiology. 1990; 36(12); 885-890. [PubMed: 2081334].
26. Ravinder et al., 2020: Ravinder M, Liao KS, Cheng YY, Pawar S, Lin TL, Wang JT, Wu CY. A Synthetic Carbohydrate-Protein Conjugate Vaccine Candidate against Klebsiella pneumoniae Serotype K2. The Journal of organic chemistry. 2020; 85(24); 15964-15997. [PubMed: 33108196].
27. Robert et al., 1981: Robert D, Michel S, Ivanoff B, Cozzone AJ, Fontanges R. On the immunogenicity of ribosomes and ribosomal proteins isolated from Klebsiella pneumoniae and Streptococcus pneumoniae. Microbiology and immunology. 1981; 25(2); 183-194. [PubMed: 7015078].
28. Robert et al., 1982: Robert D, Bienvenu P, Lafont S, Jouanneteau B, Normier G, Dussourd D'Hinterland L, Fontanges R. An attempt to localize the vaccinating power of Klebsiella pneumoniae ribosomal preparations using saccharose-gradient ultracentrifugation. Microbiology and immunology. 1982; 26(10); 941-950. [PubMed: 6761558].
29. Rodrigues et al., 2020: Rodrigues MX, Yang Y, de Souza Meira EB Jr, do Carmo Silva J, Bicalho RC. Development and evaluation of a new recombinant protein vaccine (YidR) against Klebsiella pneumoniae infection. Vaccine. 2020; 38(29); 4640-4648. [PubMed: 32444194].
30. Roe and Jones, 1984: Roe EA, Jones RJ. Vaccination against Klebsiella aerogenes. The Journal of hygiene. 1984; 93(2); 355-363. [PubMed: 6389699].
31. Roe et al., 1989: Roe EA, Jones RJ, Saunders JR. Immunoprotective extracellular polysaccharides of Klebsiella aerogenes capsular type K1, expressed in Escherichia coli. FEMS microbiology immunology. 1989; 1(5); 253-261. [PubMed: 2517220].
32. Seeberger et al., 2017: Seeberger PH, Pereira CL, Khan N, Xiao G, Diago-Navarro E, Reppe K, Opitz B, Fries BC, Witzenrath M. A Semi-Synthetic Glycoconjugate Vaccine Candidate for Carbapenem-Resistant Klebsiella pneumoniae. Angewandte Chemie (International ed. in English). 2017; 56(45); 13973-13978. [PubMed: 28815890].
33. Singh and Sharma, 2001: Singh BR, Sharma VD. Potential of Klebsiella pneumoniae cytotoxin toxoid as vaccine against klebsiellosis in rabbits and mice. Vaccine. 2001; 19(31); 4505-4510. [PubMed: 11483277].
34. Twentyman et al., 2020: Twentyman J, Morffy Smith C, Nims JS, Dahler AA, Rosen DA. A murine model demonstrates capsule-independent adaptive immune protection in survivors of Klebsiella pneumoniae respiratory tract infection. Disease models & mechanisms. 2020; 13(3); . [PubMed: 32298236].
35. Wu et al., 2020: Wu G, Ji H, Guo X, Li Y, Ren T, Dong H, Liu J, Liu Y, Shi X, He B. Nanoparticle reinforced bacterial outer-membrane vesicles effectively prevent fatal infection of carbapenem-resistant Klebsiella pneumoniae. Nanomedicine : nanotechnology, biology, and medicine. 2020; 24; 102148. [PubMed: 31887427].
|
|