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B Cell Epitopes of Four Fimbriae Antigens of Klebsiella pneumoniae: A Comprehensive In Silico Study for Vaccine Development.

ABSTRACT: Klebsiella pneumoniae is one of the major causes of nosocomial infections worldwide which can cause several diseases in children and adults. The globally dissemination of hyper-virulent strains of K. pneumoniae and the emergence of antibiotics-resistant isolates of this pathogen narrows down the treatment options and has renewed interest in its vaccines. Vaccine candidates of Klebsiella pneumoniae have not been adequately protective, safe and globally available yet. In K. pneumoniae infection, it is well known that B cells that induce robust humoral immunity are necessary for the host complete protection. Identifying the B cell epitopes of antigens is valuable to design novel vaccine candidates. In the present study using immunoinformatics approaches we found B cell epitopes of four K. pneumoniae type 1 fimbriae antigens namely FimA, FimF, FimG, and FimH. Linear and conformational B cell epitopes of each antigen were predicted using different programs. Subsequently, many bioinformatics assays were applied to choose the best epitopes including prediction antigenicity, toxicity, human similarity and investigation on experimental records. These assays resulted in final four epitopes (each for one Fim protein). These final epitopes were modeled and their physiochemical properties were estimated to be used as potential vaccine candidates. Altogether, we found four B cell epitopes of K. pneumoniae Fim antigens that are immunogen, antigenic, not similar to human peptides, not allergen and not toxic. Also, they have suitable physiochemical properties to administrate as vaccine, although their complete efficacy should be also shown in vitro and in vivo.

SUBMITTER: Zargaran FN

PROVIDER: S-EPMC7684152 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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B Cell Epitopes of Four Fimbriae Antigens of Klebsiella pneumoniae: A Comprehensive In Silico Study for Vaccine Development.

Zargaran Fatemeh Nemati FN Akya Alisha A Rezaeian Shahab S Ghadiri Keyghobad K Lorestani Roya Chegene RC Madanchi Hamid H Safaei Sadegh S Rostamian Mosayeb M

International journal of peptide research and therapeutics 20201124 2

Klebsiella pneumoniae is one of the major causes of nosocomial infections worldwide which can cause several diseases in children and adults. The globally dissemination of hyper-virulent strains of K. pneumoniae and the emergence of antibiotics-resistant isolates of this pathogen narrows down the treatment options and has renewed interest in its vaccines. Vaccine candidates of Klebsiella pneumoniae have not been adequately protective, safe and globally available yet. In K. ...[more]

PMID: 33250677

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Project description:Klebsiella pneumoniae is the predominant pathogen isolated from liver abscesses of diabetic patients in Asian countries. However, the effects of elevated blood glucose levels on the virulence of this pathogen remain largely unknown. Type 3 fimbriae, encoded by the mrkABCDF genes, are important virulence factors in K. pneumoniae pathogenesis. In this study, the effects of exogenous glucose and the intracellular cyclic AMP (cAMP) signaling pathway on type 3 fimbriae expression regulation were investigated. The production of MrkA, the major subunit of type 3 fimbriae, was increased in glucose-rich medium, whereas cAMP supplementation reversed the effect. MrkA production was markedly increased by cyaA or crp deletion, but slightly decreased by cpdA deletion. In addition, the mRNA levels of mrkABCDF genes and the activity of PmrkA were increased in Δcrp strain, as well as the mRNA levels of mrkHIJ genes that encode cyclic di-GMP (c-di-GMP)-related regulatory proteins that influence type 3 fimbriae expression. Moreover, the activities of PmrkHI and PmrkJ were decreased in ΔlacZΔcrp strain. These results indicate that CRP-cAMP down-regulates mrkABCDF and mrkHIJ at the transcriptional level. Further deletion of mrkH or mrkI in Δcrp strain diminished the production of MrkA, indicating that MrkH and MrkI are required for the CRP regulation of type 3 fimbriae expression. Furthermore, the high activity of PmrkHI in the ΔlacZΔcrp strain was diminished in ΔlacZΔcrpΔmrkHI, but increased in the ΔlacZΔcrpΔmrkJ strain. Deletion of crp increased the intracellular c-di-GMP concentration and reduced the phosphodiesterase activity. Moreover, we found that the mRNA levels of multiple genes related to c-di-GMP metabolism were altered in Δcrp strain. These indicate that CRP regulates type 3 fimbriae expression indirectly via the c-di-GMP signaling pathway. In conclusion, we found evidence of a coordinated regulation of type 3 fimbriae expression by the CRP-cAMP and c-di-GMP signaling pathways in K. pneumoniae.

Dataset Information

B Cell Epitopes of Four Fimbriae Antigens of Klebsiella pneumoniae: A Comprehensive In Silico Study for Vaccine Development.

Publications

B Cell Epitopes of Four Fimbriae Antigens of <i>Klebsiella pneumoniae</i>: A Comprehensive In Silico Study for Vaccine Development.

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