Phase-variable gene regulation in bacteria: a gambling strategy to generate diversity

Abstract

A number of bacterial pathogens contain phase-variable genes. These genes randomly switch their expression on or off, or result in expression of multiple allelic protein variants. Many of these genes encode virulence factors and potential vaccine candidates. However, inclusion of phase-variably expressed proteins in any vaccines could lead to vaccine failure; if a gene is able to randomly switch off expression, the encoded antigen will not be present, and the vaccine becomes ineffective. However, if certain phase-variable genes are highly immunogenic and highly expressed during certain disease states, they can be included in vaccines. Compounding this problem, many bacterial pathogens also encode methyltransferases that are phase-variable. Variable methyltransferase expression results in differential expression of multiple genes in systems called phasevarions (phase-variable regulons). In every characterised case, phasevarions regulate genes involved in pathogenesis, host-adaptation, and many differentially regulate putative and current vaccine candidates. Unlike individual phase-variable genes that can be identified in silico due to easily recognised genomic features, the only way to identify the genes controlled in a phasevarion is to study these systems in vitro. Including members of a phasevarion in a rationally designed vaccine would lead to the same problem as with individual phase-variable genes: random variation of protein expression could lead to vaccine failure. This talk will give an overview of our work to characterise both phase-variable gene expression and the role of phasevarions in several host-adapted pathogens, with a view to directing and informing development of new and/or improved vaccines and treatments against the bacteria encoding them.

Biography

John’s research seeks to understand random gene expression in bacterial pathogens, and to use this knowledge to improve vaccine and treatment development. John did his PhD at the University of Sheffield, UK, and post-docs in Sheffield, and at UQ in SCMB (then Molecular & Microbial Sciences) with Prof Al McEwan. He has been at Griffith since 2012, was made an associate research leader in 2019, and senior research fellow in 2021.