Identification of B‐ and T‐cell epitopes on HtrA protein of <i>Orientia tsutsugamushi</i>

Sankar, Sathish; Saravanan, Nithiyanandan; Rajendiran, Prashanth; Ramamurthy, Mageshbabu; Nandagopal, Balaji; Sridharan, Gopalan

doi:10.1002/jcb.27872

Cited by 8 publications

(11 citation statements)

References 55 publications

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“…Template modeling score (TM-score), root-mean-square deviation of atomic positions, and normalized B-factor are estimated based on C-score and protein length following the correlation observed between these qualities. 14,15 Structural validation of the protein model was done by PROCHECK program 3.5.4 which determines the stereochemical aspects along with the main chain and side chain parameters with comprehensive analysis. The model was validated using the Ramachandran plot.…”

Section: Methodsmentioning

confidence: 99%

Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas

et al. 2020

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Introduction: The emergence of new omics approaches, such as genomic algorithms to identify tumor mutations and molecular modeling tools to predict the three-dimensional structure of proteins, has facilitated the understanding of the dynamic mechanisms involved in the pathogenesis of low-grade gliomas including oligodendrogliomas and astrocytomas. Methods: In this study, we targeted known mutations involved in low-grade gliomas, starting with the sequencing of genomic regions encompassing exon 4 of isocitrate dehydrogenase 1 ( IDH1) and isocitrate dehydrogenase 2 ( IDH2) and the four exons (5-6 and 7-8) of TP53 from 32 samples, followed by computational analysis to study the impact of these mutations on the structure and function of 3 proteins IDH1, IDH2, and p53. Results: We obtain a mutation that has an effect on the catalytic site of the protein IDH1 as R132H and on the catalytic site of the protein IDH2 as R172M. Other mutations at p53 have been identified as K305N, which is a pathogenic mutation; R175 H, which is a benign mutation; and R158G, which disrupts the structural conformation of the tumor suppressor protein. Conclusion: In low-grade gliomas, mutations in IDH1, IDH2, and TP53 may be the key to tumor progression because they have an effect on the function of the protein such as mutations R132H in IDH1 and R172M in IDH2, which change the function of the enzyme alpha-ketoglutarate, or R158G in TP53, which affects the structure of the generated protein, thus their importance in understanding gliomagenesis and for more accurate diagnosis complementary to the anatomical pathology tests.

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Section: Methodsmentioning

confidence: 99%

Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas

et al. 2020

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“…They have identified B cell epitopic peptide region that was highly conserved among most prevalent serovars of Orientia tsutsugamushi and suggested its further use in the development of a highly specific and sensitive diagnostic method for scrub typhus. Further studies are required to validate the finding to sort out the problem of antigenic diversity among Orientia tsutsugamushi strains and make its diagnosis easy and reliable by improving specificity and sensitivity (Sankar et al 2019 ). The main drawback of the immuno-based methods is the lack of standardization and the choice of reference test to compare the ELISA, bring into question the validity of cut-offs used in diagnostic accuracy studies and observational studies.…”

Section: Diagnosis Of Scrub Typhusmentioning

confidence: 99%

“…Another study also shows the higher sensitivity and specificity for IgM (98.6% and 98.2%) than IgG (97.1% and 97.7%) using ICT assay (Immune Med RDT kit) with no cross-reactivity with other diseases (Diao et al 2018 ). ICT has higher sensitivity and specificity than Weil–Felix and passive Haemagglutination assay and even significantly better specificity than IFA according to Bayesian latent class models (Sankar et al 2019 ; Lim et al 2015a , b ). It has been demonstrated that the sensitivity of ICT increased by 20% when used in combination with DNA-based loop-mediated isothermal PCR assay (Blacksell et al 2012 ).…”

Section: Diagnosis Of Scrub Typhusmentioning

confidence: 99%

Diagnosis of scrub typhus: recent advancements and challenges

et al. 2020

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Scrub typhus is a mite-borne, acute febrile illness caused by the bacterium Orientia tsutsugamushi. It is a re-emerging infectious disease of the tsutsugamushi triangle. Scrub typhus is transmitted through bites of contaminated chiggers (larval stage). Diagnosis of scrub typhus is challenging as its symptoms mimic with other acute febrile illnesses. Several methods are effectual for diagnosis of scrub typhus that includes enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), immunochromatographic test (ICT), Weil-Felix, polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP). Weil-Felix test was initially used for the diagnosis of scrub typhus in underdeveloped countries but not preferred due to a lack of both specificity and sensitivity. Other immuno-based methods like IFA and ELISA are most outrank for detection of scrub typhus due to their higher sensitivity and specificity, but not vigorous to lay bare the infection at early stages and need the convalescent sampling for verification of positive samples. On another deed, PCR based methods becoming acceptable over era due to its dexterity of early-stage diagnosis with higher specificity and sensitivity but lack its applicability in circumstances of scrub typhus due to the variegated genetic makeup of Orientia tsutsugamushi among its serotypes. The present review focused on various detection methods along with their advantages and disadvantages used in the diagnosis of scrub typhus. A comparison between available methods of diagnosis with challenges in the detection of scrub typhus is also summarized.

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“…The epitope bearing peptides could be commercially synthesized and used as antigens in enzyme immune assays (EIAs) and vaccines. 12,22,23 The B-cell epitopes identi ed in our study were highly conserved among R. rickettsii; R. sibrica; R. conorii; R. typhi; R. japonica; R. prowazekii. This indicates its usefulness as suitable antigen in EIAs and vaccines for protection against both spotted fever group and typhus group of rickettsial pathogens.…”

Section: Discussionmentioning

confidence: 66%

“…MHC class-I binding T-cell epitopes (9 mers) were predicted using NetMHCpan 4.0 and IEDB Analysis Resource program. 12 HLA supertype representatives and HLA allelle reference sets were used in the respective programs. Epitopes with TAP binding e ciency and proteasomal cleavage sites along with class-I MHC binding were predicted using NetCTL 1.2 server program.…”

Section: Mhc Class-i T-cell Epitope Predictionmentioning

confidence: 99%

Identification and Computational Validation of TolC Derived B- and T- Cell Epitopes for the Development of Pan-Rickettsial Vaccine

Sankar

Subramanian

Venkatesan³

2022

Preprint

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Introduction: Rickettsia is vector-borne causing Rickettsial infections with high mortality. Currently, no vaccines are available for the prevention of rickettsioses. The study aims to identify B- and T- cell epitopes to peptides derived from TolC protein of rickettsial group of pathogens. Immunogenic linear B-cell epitopes and MHC class I and II T-cell epitopes predicted from the consensus sequences of TolC protein for each rickettsial species. The putative antigenic epitopes may trigger an effective immune response and prove to be a novel vaccine that protects against all rickettsial infections. Methods: MHC class-I binding T-cell epitopes were predicted along with TAP binding efficiency and proteasomal cleavage sites. Molecular docking study was carried out to investigate the binding affinity between the MHC-I protein molecules with the peptides. The MHC-peptide complex with the highest RMSD score was further used for molecular dynamic simulation study.Results: Three B-cell candidate peptide epitopes were selected, of which epitope IYPEGGAQYSRIRSAKNQTRNSA/VVQ is conserved across both typhus group and spotted fever group of rickettsial species was considered best suitable for candidate vaccine. The peptide epitope KLYEAKITR had a good RMSD score as well as promiscuous binding to 28 different HLA allele supertypes and was considered suitable for the development of subunit peptide vaccine. Conclusion: The B- and T- cell candidate peptide epitopes identified in our study would elicit B- and T-cell immune responses respectively and serve as a novel candidate peptide vaccine.

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Identification of B‐ and T‐cell epitopes on HtrA protein of Orientia tsutsugamushi

Cited by 8 publications

References 55 publications

Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas

Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas

Diagnosis of scrub typhus: recent advancements and challenges

Identification and Computational Validation of TolC Derived B- and T- Cell Epitopes for the Development of Pan-Rickettsial Vaccine

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