TUNG LE LABORATORY

Horizontal gene transfer & GTAs

Horizontal gene transfer is especially widespread in bacteria and is one of the major mechanisms by which bacterial genomes evolve and adapt. Understanding horizontal gene transfer and how new genetic information is incorporated and domesticated into the existing signalling network and physiology of the host is a fundamental problem in biology. Horizontal gene transfer also contributes to the spread of antimicrobial resistance, which is a leading cause of mortality worldwide. Compared to well-studied horizontal gene transfer mechanisms, such as transformation, conjugation, and transduction, virus-like gene transfer agents (GTA) are poorly understood.

 

GTAs (Fig. 1A) are peculiar virus-like particles that were domesticated from ancestral bacterial viruses to now serve as nanomachines for the host bacteria. GTAs package and disseminate DNA of the host bacteria (Fig. 1A). Upon the activation of GTA production, the genome of the host bacteria is fragmented into ~4-15 kb DNA which is packaged randomly into newly assembled GTA particles. The host is then lysed to release the particles which transfer packaged DNA into recipient cells (Fig. 1A-B).

 

GTAs are distinct from traditional bacterial viruses/bacteriophages because they package random DNA from the bacterial host rather than their own DNA, which is invariably larger than the maximum DNA fragment size that can be packaged, meaning that GTAs cannot self-replicate nor be infectious.

 

The presence of GTAs in taxonomically diverse bacteria, including many pathogens, presents an excellent opportunity to study the fascinating biology and fundamentals of domestication of genetic information, and to engineer GTA for biotechnological or therapeutic purposes in the future.