Transcriptional antitermination integrates the expression of loci of diverse phage origin in the chimeric Bartonella Gene Transfer Agent BaGTA

Gene Transfer Agents (GTAs) are mobile genetic elements derived from bacteriophages that mediate genome-wide horizontal gene transfer (HGT) in diverse groups of prokaryotes. BaGTA, encoded by all the pathogens of the genus Bartonella, is a chimeric GTA that evolved by the domestication of two phages. The run-off-replication module ROR of one phage is integrated with the capsid production, DNA packaging and lysis machinery Bgt of a second phage. Restricted to a self-sacrificing subset of the bacterial population, the position-specific DNA amplification and packaging of a genomic plasticity region enriched for genes involved in host interaction and adaptation selectively enhances the HGT frequency of these pathogenicity genes. This feature of BaGTA is considered a key innovation underlying the evolutionary success of Bartonella. Little is known, however, about the mechanism mediating the coordinated expression of the ror and bgt loci. Here, we established the regulatory hierarchy, with ror acting upstream of the capsid gene cluster bgtA-K. BrrG, encoded by the ror locus, controls the transcription of the bgtA-K operon by functioning as a processive antiterminator. This study provides the first insights into the mechanism controlling the coordinated expression of the two BaGTA modules of divergent phage origin. Beyond BaGTA, we propose that antitermination is a broadly relevant mechanism for controlling HGT by GTAs of the Alphaproteobacteria.