Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2014

Phasevarions as regulators of bacterial adaptation and virulence (#59)

Luke V Blakeway 1 , Peter M Power 1 , Freda E-C Jen 1 , Sam R Worboys 1 , Matthew Boitano 2 , Tyson A Clark 2 , Jonas Korlach 2 , Lauern O Bakaletz 3 , Michael P Jennings 1 , Ian R Peak 1 , Kate L Seib 1
  1. Institute for Biomedicine and Glycomics, Griffith University, Gold Coast, QLD, Australia
  2. Pacific Biosciences, Menlo Park, CA, USA
  3. Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA

Moraxella catarrhalis is an asymptomatic colonizer of the nasopharynx, and is also a significant cause of otitis media and exacerbations of chronic obstructive pulmonary disease. However, the triggers or markers of a switch from carriage to a disease state are unclear. Phase variation (high-frequency reversible ON/OFF random switching) of gene expression is a common feature of host-adapted bacterial pathogens. Our studies have identified phase variable N6-adenine DNA methyltransferases in a range of pathogens, including M. catarrhalis1, Neisseria meningitidis and Neisseria gonorrhoeae2, 3, that control the random coordinated switching of expression of multiple genes. These systems constitute phase variable regulons, called phasevarions, which enable the bacteria to randomly switch between distinct phenotypes.         

We have recently characterized a phase variable DNA methyltransferase (ModM) from M. catarrhalis that controls a phasevarion. Three modM alleles have been identified (modM1-3) that differ in their DNA recognition domain. ModM2 occurred in the majority of strains. However, modM3 is over-represented in isolates from the middle ear, suggesting a role for this allele in disease compared to carriage. Using single molecule, real-time (SMRT) genome sequencing and methylome analysis we have determined the ModM2 methylation target, and proteomic analyses show that ModM2 regulates expression of multiple genes with potential roles in colonization, infection and protection against host defences.

  1. Seib KL, Peak IR, and Jennings MP. (2002) Phase variable restriction-modification systems in Moraxella catarrhalis. FEMS Immunology and Medical Microbiology. 14;32(2):159-65.
  2. Srikhanta YN, Dowideit SJ, Edwards JL, Falsetta ML, Wu HJ, Harrison OB, Fox KL, Seib KL, Maguire TL, Wang AH, Maiden MC, Grimmond SM, Apicella MA, Jennings MP. (2009) Phasevarions mediate random switching of gene expression in pathogenic Neisseria. PLoS Pathogens. 5(4):e1000400.
  3. Seib KL, Pigozzi E, Muzzi A, Gawthorne JA, Delany I, Jennings MP, Rappuoli R. (2011) A novel epigenetic regulator associated with the hypervirulent Neisseria meningitidis clonal complex 41/44. FASEB Journal. 25(10):3622-33.