A wide variety of bacterial pathogens contain phase-variable methyltransferases, that control expression of multiple genes via epigenetic mechanisms. These phase-variable regulons – phasevarions – regulate genes involved in pathogenesis, host-adaptation, and many lead to alteration of antibiotic resistance. Many phasevarions also lead to differential regulation of putative and currently investigated vaccine candidates. For vaccines to be effective, they require that their targets are stably expressed. Individual phase-variable genes are able to be identified in silico as they contain easily recognised features. Phasevarions complicate the rational design of vaccines as the genes they regulate do not contain any identifiable features. The presence of phase-variable methyltransferases that result in large scale expression differences in bacterial populations have until now not been investigated when developing vaccines and/or novel therapeutic targets.
Our studies provide a framework for the rational design of vaccines and treatments against organisms containing phasevarions by identifying the stably expressed protein repertoire of these bacteria. This will result in highly efficient, cost effective treatments /therapies /preventative measures.