Asymmetric plasmid partitioning (APP) is a synthetic genetic circuit that controls asymmetric cell division in Escherichia coli. The technique was inspired by stem cell division and causes E. coli progenitor cells to divide in a way that produces one differentiated daughter cell and one retaining the original phenotype.
Researchers Matthew Bennet and Sara Molinari at Rice University created a genetic circuit that produces genetically distinguished cells in Escherichia coli as the bacterium divides. The process can be controlled to create diverse communities of microbes that show complex, non-native behaviors. It is a synthetic biology approach that was inspired by asymmetric cell division in stem cells and the development of multicellular organisms with different cell populations.
Plasmid DNA is a circular genetic structure that can replicate independently from chromosomes, and can contain genes that provide bacteria with genetic advantages such as antibiotic resistance. Normally DNA plasmids are passed on to both daughter cells upon cell division, either by there being lots of plasmids or by a mechanism where they are actively pulled into each new daughter cell. For APP, plasmids were engineered to aggregate in a cluster so that they do not distribute homogeneously during cell division. Instead they are inherited by only one of the two daughter cells. The daughter cells that receive the plasmids remain identical to the progenitor cells but daughter cells that do not receive plasmids become genetically distinct. For aggregating plasmids, the researchers used a ParB protein to bind a parS sequence on the target plasmids so they form a single nucleoprotein complex.
Motility was tied to differentiation, which allowed physical separation of the genetically distinct cells. In their paper, Molinari et al. characterize an orthogonal inducible circuit that enables simultaneous partitioning of two plasmid species which results in cells with four distinct differentiated states. The APP system is a step towards engineering multicellular systems from prokaryotic hosts.
