Heterologous Expression of Pneumococcal Surface Antigen PsaA Gene
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Title |
Heterologous Expression of Pneumococcal Surface Antigen PsaA Gene
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Creator |
PATEL, NAFISABANU A.
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Contributor |
MAHATMA, LALIT
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Subject |
proteins, diseases, bacteria, biological phenomena, genes, amino acids, sampling, dna, enzymes, vegetables
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Description |
Attempts were made to isolate Streptococcus pneumoniae from the clinical samples. The clinical samples procurred from different laboratories included sputum, blood, throat swab, bronchial and tracheal aspirate. Typical cocci shaped organisms occurring in pair ar e character ised, Gram positive reaction, alpha haemolysis, inability to produce effervescence of CO2 in catalase test, susceptibility to optochin and bile solublization were the basic tests performed for the identification and characterization of S. pneumoniae. By the basic tests and VITEK test, three isolates AML-4, AML-7 and ADL-1 wer e identifiedand char acter ized to be S. pneumoniaewhere as the other three alpha haemolytic streptococci ( ADL-2, AML-3 AND AML-10) were identified as S. viridian and the other three isolates showieg beta haemolysis were of other streptococci groups. S. pneumoniae synthesize at least four different antigens produced by the surface of the bacteria commonly known as Pneumococcal surface antigens (Psa) which includes PsaA, PsaB, PsaC and PsaD. Bacter ia also have surface proteins known as Pneumococal surface proteins. The resu lts of Pairwise sequence alignment indicates PsaA gene is highly conserved as compared to the PspA gene. The amino acid composition of PsaA protein contained Maximum content of lysine in the range of 40 residues, while the PspA protein co ntained 90 residues of Alanine and 87 residues of Glutamine. PspA protein had large amount of negativel y charged residues (121 aminoacids) while the PsaA protein had just 49 such r esidues. The estimated half life of both the proteins in reticulocytes (in-vitro) was approximately 30 hours, in yeast it was greater than 20 hours and in E. coli it was more than 10 hours. The result of stabilit y analysis indicated that PsaA protein had 72.61% stabilit y which was higher than the stabilit y index of PspA (58.19% stabilit y). Major hydrophobicit y region of PsaA protein was between the aminoacid positions 170-180. While the PspA protein graph interpreted the hydrophobic region cover ing a larger part of the protein associated between the regions 110-120 and then beginnign from the aminoacid 180 till 600 aminoacids. Out of the 26 MHC ligand s predicted for PspA protein, 22 epitopic sites lies between 200-630 aminoacids scoring PsaA protein as more stable than the PspA protein. The number of MHC ligands identified in PsaA protein was 7, lying at amino acid positions 61,78,79,118,202,266 and 290. No epitope had the mutable site for PsaA protein. Looking at the results of bioinformatics it was concluded that the PsaA gene is better choice for the immuno genicit y. hydrophobicit y, maximum score of bulkiness and mutabilit y score indicated that the PsaA gene is better choice for the immuno genicit y. DNA could be extracted by the CTAB method with slight modification. In PCR the temperature gradient of higher temperature from 46ºC and above did not result into amplification of PsaA gene. The best amplification was observed at 45.4 ºC. 1.0 mM concentration of MgCl2 was found best for the specific amplification of PsaA gene. The concentration of PCR product in the range of 50ng resulted into positive ligation. The overnight incubation of the ligation mixture at 4ºC incr eased the rate of positive ligation reaction. DH5α stain of E.coli was used for transformation of PsaA gene. Transformation of E.coli was performed on the plates containing Ampicillin and X-gal and kept for incubation. The ratio of 1:3 of vector to the PsaA gene resulted into increased transformation efficiency. The r esults of controlled plate and transformation with sample 1 and sample 2 showed the presence of transformed colonies and successful cloning of PsaA gene into E.coli. Single digestion wit h Kpn1 linear ized the plasmid giving a band of 4 kb. Crude protein was extracted from the transformed cells and analysed for the expression of PsaA protein. SDS-PAGE showed the presence of bands of PsaA proteins of of 40 kDa indicating heterologous expressio n of PsaA in E.coli. For the effective sterilization treatment of leaves for 4 minutes with the mercuric chloride was found most appropriate. For in vitro regeneration of tomato, basal MS media fortified with 1.25 mg/l BAP+ 0.50 mg/l IAA showed the best results in terms of callus induction (86.67 %), days taken for the callus initiation (8.33 days), days taken for shoot initiation ( 26 days of inoculation) and the number of shoots formed (7.67). For shoot regeneration and multiplication 2 mg/l BAP + 1mg/l IAA) gave the highest response in terms of 61.11%, and the number of shoots produced were 11 as well as the highest shoot length of 5.17 cm. Subculturing effectively leads to increase in the number as well as the length of shoots. The third subculture showed an increase in the number of shoots regenerated to be nearly 12 as well as increase in the shoot length to 5.90 cm. Rooting parameters were significantl y influenced by the types and concentrations of Auxin and the strength of MS medium. Half str ength MS medium supplemented with 0.1 mg/l NAA (T4) recorded significantly minimum days to initiate the root (7 days), maximum rooting per cent (70 %) and number of root also higher. The combination of half MS with the hormone concentr ation of 0.50 mg/l IBA also gave better rooting. During the hardening maximum survival (61 %) of plantlets with minimum days for new sprouting (11.25 days) was reported in Vermicompost : soil mixture. Since the gene is highly conservative, this would be available in all the serot ypes and strains of the pathogen. High stabilit y, availab ilit y of all the epitopes on the surface, high antigenicity, long retention time in Prokaryotes and Eukaryotes system further support the hypothesis that it would not be digested by the phagocytes and will be exposed to carry out the stimulation of immune system and all the immuno genic sites will be exposed to the lymphocytes for the production of systemic and specific antibodies against the prevailing as well as newly emerging strains and serotypes of S. pneumoniae. The expression of PsaA gene in the tomato and its comsumption would elicit the immune system and stimulate the humoral immune response against Streptococcus pneumoniae. This approach would help in the prevention and eradication of highly fatal disease of human decreasing the child mortalit y and increasing the life expectanc y. |
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Date |
2016-05-04T11:19:20Z
2016-05-04T11:19:20Z 2013-07 |
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Type |
Thesis
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Identifier |
http://krishikosh.egranth.ac.in/handle/1/65778
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Language |
en
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Format |
application/pdf
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Publisher |
Navsari Agricultural University, Navsari
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