Interbacterial signaling via Burkholderia contact-dependent growth inhibition proteins

In prokaryotes and eukaryotes, cell-cell communication and recognition of self are critical to coordinate multicellular functions. While kin and kind discrimination are increasingly appreciated to shape naturally occurring microbe populations, the underlying mechanisms that govern these interbacterial interactions are insufficiently understood. Here we identify a mechanism of interbacterial signal transduction that is mediated by contact-dependent growth inhibition (CDI) system proteins. CDI systems have been characterized by their ability to deliver a polymorphic protein toxin into the cytoplasm of a neighboring bacterium, resulting in growth inhibition or death unless the recipient bacterium produces a corresponding immunity protein. Using the model organism Burkholderia thailandensis, we show that delivery of a catalytically active CDI system toxin to immune (self) bacteria results in gene expression and phenotypic changes within the recipient cells. Termed contact-dependent signaling (CDS), this response promotes biofilm formation and other community-associated behaviors. Examination of wild-type Burkholderia thailandensis and two mutant strains, each in triplicate (9 samples total). mutant BtEKA contains two amino acid substitutions (E3064A and K3066A) within the coding sequence of gene Bth_I2723. In mutant PS12-WT, the native promoter of gene Bth_I2723 has been replaced with the strong constitutive promoter of the E264 rpsL gene, PS12.