Pneumococcal Phasevarions Control Multiple Virulence Traits, Including Vaccine Candidate Expression

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dc.contributor.authorPhillips, Z.N.
dc.contributor.authorTrappetti, C.
dc.contributor.authorVan Den Bergh, A.
dc.contributor.authorMartin, G.
dc.contributor.authorCalcutt, A.
dc.contributor.authorOzberk, V.
dc.contributor.authorGuillon, P.
dc.contributor.authorPandey, M.
dc.contributor.authorvon Itzstein, M.
dc.contributor.authorSwords, W.E.
dc.contributor.authorPaton, J.C.
dc.contributor.authorJennings, M.P.
dc.contributor.authorAtack, J.M.
dc.contributor.editorLaRock, C.N.
dc.date.issued2022
dc.descriptionPublished online 10 May 2022
dc.description.abstractStreptococcus pneumoniae is the most common cause of bacterial illness worldwide. Current vaccines based on the polysaccharide capsule are only effective against a limited number of the .100 capsular serotypes. A universal vaccine based on conserved protein antigens requires a thorough understanding of gene expression in S. pneumoniae. All S. pneumoniae strains encode the SpnIII Restriction-Modification system. This system contains a phase-variable methyltransferase that switches specificity, and controls expression of multiple genes—a phasevarion. We examined the role of this phasevarion during pneumococcal pathobiology, and determined if phase variation resulted in differences in expression of currently investigated conserved protein antigens. Using locked strains that express a single methyltransferase specificity, we found differences in clinically relevant traits, including survival in blood, and adherence to and invasion of human cells. We also observed differences in expression of numerous proteinaceous vaccine candidates, which complicates selection of antigens for inclusion in a universal protein-based pneumococcal vaccine. This study will inform vaccine design against S. pneumoniae by ensuring only stably expressed candidates are included in a rationally designed vaccine.
dc.description.statementofresponsibilityZachary N. Phillips, Claudia Trappetti, Annelies Van Den Bergh, Gael Martin, Ainslie Calcutt, Victoria Ozberk, Patrice Guillon, Manisha Pandey, Mark von Itzstein, W. Edward Swords, James C. Paton, Michael P. Jennings, John M. Atack
dc.identifier.citationMicrobiology Spectrum, 2022; 10(3):1-17
dc.identifier.doi10.1128/spectrum.00916-22
dc.identifier.issn2165-0497
dc.identifier.issn2165-0497
dc.identifier.orcidTrappetti, C. [0000-0001-8272-0068]
dc.identifier.orcidPaton, J.C. [0000-0001-9807-5278]
dc.identifier.urihttps://hdl.handle.net/2440/135497
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.relation.granthttp://purl.org/au-research/grants/arc/DP180100976
dc.relation.granthttp://purl.org/au-research/grants/arc/DP190102980
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1071659
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1174876
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1138466
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1160379
dc.rightsCopyright © 2022 Phillips et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
dc.source.urihttps://doi.org/10.1128/spectrum.00916-22
dc.subjectphasevarion
dc.subjectphase variation
dc.subjectStreptococcus pneumoniae
dc.subjectvaccine
dc.subjectepigenetic regulation
dc.subjectpneumococcus
dc.titlePneumococcal Phasevarions Control Multiple Virulence Traits, Including Vaccine Candidate Expression
dc.typeJournal article
pubs.publication-statusPublished

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