Modulation of the host transcriptome by Coxiella burnetii nuclear effectors

Abstract

Coxiella burnetii is an infectious bacterium that causes Q-fever in mammals. Central to pathogenesis is a Dot/Icm Type IV secretion system (T4SS) which is similar to the secretion system of other pathogens. The proteins secreted by the T4SS are essential for modulating certain cellular processes such as apoptosis, intracellular replication and vacuole formation. It was hypothesized that these proteins accomplished these functions by binding to the host cell's nuclear genome. Chromatin Immunoprecipitation (ChIP) was used to determine which nuclear T4SS proteins bound to host DNA. The immunoprecipitated DNA was sequenced to determine what genes were present and their function within the host cell. Sequencing revealed that Cbu1314 bound host genes associated with important cell functions such as cell-cell signaling, apoptosis, and regulation of the cell cycle. The modification of these genes could lead to an incomplete host response and allow the continued replication of C. burnetii. These results suggest that the nuclear effector Cbu1314 binds host DNA and may modulate the host response by manipulation of host chromatin.