Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design
| Autor: | Mumtaz Virji, Clio A. Andreae, Darryl J. Hill, Richard B. Sessions |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Bacterial Diseases
0301 basic medicine lcsh:Medicine Meningococcal Disease Neisseria meningitidis Pathology and Laboratory Medicine medicine.disease_cause Biochemistry Database and Informatics Methods Antigenic Diversity Medicine and Health Sciences Post-Translational Modification lcsh:Science Genetics Vaccines Multidisciplinary Antigenic Variation Recombinant Proteins Bacterial Pathogens Infectious Diseases Medical Microbiology Neisseria Pathogens Sequence Analysis Signal Peptides Bacterial Outer Membrane Proteins Research Article Infectious Disease Control Bioinformatics 030106 microbiology Meningococcal Vaccines Sequence alignment Meningitis Meningococcal Biology Research and Analysis Methods Meningococcal disease Microbiology Bacterial genetics 03 medical and health sciences Amino Acid Sequence Analysis Antigen Sequence Motif Analysis medicine Humans Amino Acid Sequence Adhesins Bacterial Microbial Pathogens Antigens Bacterial Bacteria lcsh:R Organisms Computational Biology Genetic Variation Biology and Life Sciences Proteins medicine.disease biology.organism_classification Bacterial adhesin 030104 developmental biology lcsh:Q Sequence Alignment |
| Zdroj: | Andreae, C, Sessions, R, Virji, M & Hill, D 2018, ' Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design ', PLoS ONE, vol. 13, no. 3, 193940 . https://doi.org/10.1371/journal.pone.0193940, https://doi.org/10.1371/journal.pone.0193940 PLoS ONE, Vol 13, Iss 3, p e0193940 (2018) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis. |
| Databáze: | OpenAIRE |
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