From predator to partner: investigation of molecular mechanisms and function of "Bartonella" Gene Transfer Agent

Gene Transfer Agents are mobile genetic elements mediating horizontal gene transfer in diverse groups of prokaryotes. GTAs originate from bacteriophages and represent a type of rudimentary, domesticated phages endogenized and utilized by prokaryotes. Five distinct types of GTAs are known that share no common origin and represent an example of convergent evolution. GTAs transfer random bacterial genes however the function of GTAs remains debatable. This is associated with the lysis-driven release of GTAs from the producing cells ultimately leading to cellular death. Such a bacterial companion imposes a fitness cost on the host bacterium and would not be selected unless it provides a benefit that balances the cost.
In this work, I investigate the role of the Bartonella Gene Transfer Agent, or BaGTA, in the lifestyle of Bartonella. In contrast to other known GTAs, BaGTA has two separate functional modules: ROR enabling a position-specific amplification of the transferred DNA and BaGTA machinery for its packaging and transfer. This mechanism is a highly conserved feature of pathogens of the genus Bartonella. Moreover, it is suggested to be one of the key innovations underlying their evolutionary success.
In the published Research article I, we investigated an immunogenic surface protein and identified that it is a highly dynamic autotransporter essential for the infection. I use this autotransporter and specific antibodies as tools to address the BaGTA function in the pathogenesis of Bartonella.
I further go into the molecular details of BaGTA functioning and address the interplay of BaGTA with ROR. In Research article II, we investigate the genetic network enabling the coordination of these two distinct components. We found that the ROR encodes a set of regulatory proteins that control the expression of the BaGTA locus. The control is achieved by premature termination of the BaGTA locus transcription and BrrG-mediated processive antitermination. We proposed that additional regulators are involved in controlling BaGTA and speculated about the potential universality of processive antitermination in alphaproteobacterial GTA. We outlined the potential direction for further investigations. Bartonella and BaGTA constitute an interesting model which provides insights into the evolution of pathogens shaped by GTA. GTAs are present in distinct lineages of both bacteria and archaea, and are prevalent in up to 60% of alphaproteobacterial genomes. Thus, GTAs claim to be a widespread mechanism of HGT whose full potential, we believe, is yet to be uncovered.