We recently posted an update on horizontal gene transfer (HGT) to highlight the existence of strategies used by bacteria to exchange DNA – in addition to those traditionally acknowledged, that is transformation, transduction and conjugation. One of these more recently recognized mechanisms involves entities called gene transfer agents (GTAs).
GTAs are puzzling elements. First, they look like phages but do not self-propagate. The genes involved in producing GTAs resemble those of prophages, which sometimes confounds their identification in sequenced genomes. GTAs package DNA from the host genome, but the size encapsulated is usually smaller than that of the corresponding GTA-encoding gene cluster. The resulting particles carry fragments of host DNA but not necessarily the genes needed for self-transmission. Secondly, cells that produce these GTAs, which are a small percentage of the population, lyse and die. The released phage-like particles then carry the encapsulated small fragments of host dsDNA to other cells. GTAs are marvelous vehicles of gene transfer, but they also represent a dead end both for themselves and for the producing cell.
GTAs were discovered in the 1970's and shown to mediate gene transfer in the bacterium Rhodobacter capsulatus. Over the years GTAs were found in other bacteria and in archaea, adding pieces to the puzzle of their existence and function. However, some fundamental questions are still unanswered. The genes for these elements are conserved across organisms and have been retained in somemicrobial genomes for millions of years, meaning that they must be relevant to the host cell. It is easy to understand the advantage to the population of moving genetic information between cells, but the benefit for the producing cell, which dies in the process, is unclear. Why then do these elements still exist in microbial genomes?
A recent study conducted by Kevin Gozzi and colleagues from the John Innes Centre and MIT provides some surprising answers. Unexpectedly, they come from studying the bacterium Caulobacter crescentus, long used as a model organism for understanding cell differentiation and the cell cycle, but not known to produce GTAs. When analyzing a strain that lacked a repressor (called RogA) they stumbled upon a cluster of overexpressed genes putatively encoding a GTA element. They then confirmed that these genes produced GTA particles that were released by the bacterium and transferred genetic material to recipient cells. But what is the effect of this gene transfer? To begin with, cells that overproduced GTAs survived better during long-term incubation in stationary phase. More interestingly, this survival was tied to fixing DNA damage. Clever mixing experiments, done by combining GTA producers and recipient cells in which they induce DNA damage, indicated that the transferred DNA was important for the recipient cell's ability to survive damage caused by double strand DNA breaks, a lesion that is difficult to repair and highly lethal.
This work shows that GTAs produced by C. crescentus help cells overcome the lethal effect of DNA damage. Whether this role is relevant to other microbes, or is used in the wild, remains to be determined. Nonetheless, GTAs are another example of the importance of gene exchange in microbial systems.