Dr Jo Stevens

The Roslin Institute

Research Interests

The melioidosis pathogen Burkholderia pseudomallei is a facultative intracellular pathogen of humans and animals that enters non-phagocytic cells, escapes from endosomes and propels itself within and between cells by continuous polymerisation of actin at one bacterial pole (known as actin based motility). Actin-based motility is also a feature of infection by the closely related glanders pathogen B. mallei and the avirulent saprophyte B. thailandensis.

With previous BBSRC support, I have unravelled how B. pseudomallei stimulates actin assembly to propel itself within and between eukaryotic cells. I characterised a factor required for intracellular actin-based motility (BimA), surveyed its diversity in natural populations and identified functional orthologues in other Burkholderia species . BimA is required for intracellular survival, intercellular spread and virulence and acts in a manner distinct from most other pathogen-associated factors required for actin-based motility. Moreover, I recently found that BimA from closely-related Burkholderia species use distinct strategies to nucleate actin. B. thailandensis BimA recruits and activates a cellular complex that assembles actin (Arp2/3) via a unique central acidic domain, whereas B. pseudomallei BimA exhibits an intrinsic Arp2/3-independent ability to nucleate actin in a manner akin to eukaryotic formin- and spire-family proteins.

My ongoing research is aimed at further understanding the mechanisms by which BimA proteins from related Burkholderia species function as actin nucleators. Towards this aim I am trying to understand how posttranslational modifications of the proteins affect function as well as define any differences in the host cell proteins they may interact with. I am also investigating the role of BimA and actin-based motility in the evasion of intracellular recognition and killing mechanisms in host cells.

 

Selected Publications

  • Chayada Sitthidet, Joanne M. Stevens, Terence R. Field, Abigail N. Layton, Sunee Korbsrisate, Mark P. Stevens. 2010. Actin-Based Motility of Burkholderia thailandensis Requires a Central Acidic Domain of BimA That Recruits and Activates the Cellular Arp2/3 Complex. Journal of Bacteriology Vol: 192 Pages: 5249-5252. More»
  • Chayada Sitthidet, Sunee Korbsrisate, Abigail N. Layton, Terence R. Field, Mark P. Stevens, Joanne M. Stevens. 2011. Identification of Motifs of Burkholderia pseudomallei  BimA Required for Intracellular Motility, Actin Binding, and Actin Polymerization. Journal of Bacteriology Vol: 193 Pages: 1901-1910. More»
  • C. Sitthidet, J. M. Stevens, N. Chantratita, B. J. Currie, S. J. Peacock, S. Korbsrisate, M. P. Stevens. 2008. Prevalence and sequence diversity of a factor required for actin-based motility in natural populations of Burkholderia species. Journal of Clinical Microbiology Vol: 46 Pages: 2418-2422. More»