Abstract
Although evolutionarily distant, the bacteria Listeria monocytogenes, Shigella flexneri, and Burkholderia thailandensis each undergo a "cell-to-cell" spreading process that allows these pathogens to disseminate within human tissues. Spread initiates when bacteria polymerize actin filaments that propel them through the host cell cytosol. The pathogens then remodel the plasma membrane into protrusions that are internalized by adjacent cells and resolved into double membranous vacuoles (DMVs) which lyse to liberate bacteria. In this review, we discuss recent publications indicating that L. monocytogenes, S. flexneri, and B. thailandensis each enhance their spread by altering the subcellular localization of human Dynamin 2-a GTPase that regulates endocytosis and other trafficking pathways. Interestingly, Dynamin 2 controls distinct steps in spread of L. monocytogenes, S. flexneri, and B. thailandensis. In the case of L. monocytogenes, the GTPase has the potential to restrict protrusion formation by generating tension at tight junctions. However, L. monocytogenes secretes a protein that relieves this restriction of protrusions, allowing efficient spread. During dissemination of S. flexneri and B. thailandensis, Dynamin 2 is co-opted to resolve protrusions into DMVs. B. thailandensis also mobilizes Dynamin 2 to lyse DMVs. These findings highlight diverse ways in which bacteria control Dynamin 2 to augment spread.