Pneumococcal Phasevarions Control Multiple Virulence Traits, Including Vaccine Candidate Expression
Date
2022
Authors
Phillips, Z.N.
Trappetti, C.
Van Den Bergh, A.
Martin, G.
Calcutt, A.
Ozberk, V.
Guillon, P.
Pandey, M.
von Itzstein, M.
Swords, W.E.
Editors
LaRock, C.N.
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Microbiology Spectrum, 2022; 10(3):1-17
Statement of Responsibility
Zachary 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
Conference Name
Abstract
Streptococcus 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.
School/Discipline
Dissertation Note
Provenance
Description
Published online 10 May 2022
Access Status
Rights
Copyright © 2022 Phillips et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.