Poster Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

Phasevarions of pathogenic bacteria – widely distributed epigenetic regulators that evolved independently from distinct classes of restriction-modification systems  (#101)

John M. Atack 1 , Lauren O. Bakaletz 2 , James C. Paton 3 , Michael P. Jennings 1
  1. Griffith University, Gold Coast, QLD, Australia
  2. Nationwide Children's Hospital, , Ohio, USA, Columbus, OH, United States
  3. Research Centre for Infectious Diseases, University of Adelaide, Adelaide, SA, Australia

Phasevarions (for phase variable regulons) have emerged as gene regulation systems in many bacterial pathogens. Phase-variation is the rapid and reversible variability of gene expression, and can be mediated by a variety of mechanisms. Variation in the number of gene associated simple sequence repeats (SSRs), or homologous recombination between variable expressed and silent gene loci are two of the most common mechanisms. Phasevarions are controlled by the phase-variation of methyltransferases that are part of restriction-modification (R-M) systems, classically associated with bacteriophage defence. We have recently described these systems in two highly relevant human pathogens – Streptococcus pneumoniae, and non-typeable Haemophilus influenzae (NTHi). The pneumococcal system is controlled by a type I R-M system that shuffles between six variable specificities by homologous recombination between multiple copies of the gene encoding the type I system specificity protein. The system in NTHi is controlled by a type III methyltransferase that switches between two states due to SSR variation resulting from polymerase slippage during replication. SSR variation leads to ON (expressed) and OFF (not expressed) methyltransferase states, the OFF resulting from a frame shift and a premature stop codon in the alternate reading frame. Analysis of several bacterial pathogens reveals: 1) a high prevalence of these systems in both gram-positive and gram-negative bacterial pathogens; 2) a wide variety of mechanisms used to generate methyltransferase diversity and phase variation; and 3) the potential for distinct phenotypes resulting from this switching. This work will describe the progress made to date to dissect these systems in several bacteria where phasevarions have never been described, and in bacterial pathogens where newly discovered phasevarions add an extra level of complication to discovering stably expressed proteins for use in vaccines and as novel treatment targets.