MIT research details parasitic battles

Scientists at MIT and the Technion Israel Institute of Technology have for the first time recorded the entire genomic expression of both a host bacterium and an infecting virus over the eight-hour course of infection.  

The work, reported in the Sept. 6 issue of Nature, likely will encourage scientists in several fields to rethink their approach to the study of host-virus systems. Such systems are believed to play a key evolutionary role by facilitating the transfer of genes between species.  

Professors Debbie Lindell of the Technion and Sallie Chisholm of MIT and co-authors say that their study of a system involving the marine bacteria, Prochlorococcus, leads them to speculate that viral infection may play a role in shaping the genetic repertoire of families of bacteria, even though individual infected bacteria die.  

This could indicate that the meeting between a marine bacterial host and its virus may not be just a battle between two individuals, but an evolutionarily significant exchange that helps both species become more fit for life in the ocean environment.

"The current status of host-virus relations has been influenced by a rich history of interactions," said Lindell, who conducted the research as a postdoctoral associate in Chisholm's lab before joining the Technion faculty in late 2006. "While we can't definitively pin down the sequence of past co-evolutionary events, our findings suggest a novel means through which the exchange of beneficial genes between host and virus have been triggered."  

And, because the pattern of genomic expression in this host-virus system differed significantly from that in the more commonly studied system of intestinal bacteria such as E. coli and a virus called T7, the research will likely lead to increased appreciation for the need to study diverse types of marine bacteria, rather than relying on a single system as a broad model.  

"We hope this work will encourage scientists to explore a wide range of host-pathogen systems and thus lead to a significant broadening of our understanding of the diversity of the host-pathogen interactions existing in nature," said Chisholm, the Lee and Geraldine Martin Professor of Environmental Studies, who holds appointments in the Department of Civil and Environmental Engineering (CEE) and the Department of Biology.

In previously studied host-virus systems, a virus hijacks the bacterial host cell and shuts down genome expression immediately, preventing the bacterium from conducting its own metabolic processes. The attacking virus redirects expression to its own genome and activates the genes beneficial for its activity.  
But uncharacteristically, in the system of Prochlorococcus and virus P-SSP7, an unprecedented 41 of the bacteria's 1,717 genes were upregulated. That is, the researchers detected increased quantities of the messenger RNA encoded by these genes in the cell during the infection process. The upregulation of so many host genes during infection is a phenomenon unseen before in the world of bacteriology.  

Lindell and Chisholm believe the most plausible scenario to explain this is that the bacterium activates certain genes in response to infection as a means of self-protection. The virus has "learned" to use those genes to its own advantage and so incorporates them into its own genome. Later, when infecting another bacterium, the virus upregulates those genes itself to facilitate its own reproduction within the host bacterium. When a bacterium survives an infection, those viral modified genes are incorporated back into the bacterial DNA, making that bacterium and its descendants more likely to survive in the harsh ocean environment.  

Other MIT authors are graduate students Gregory Kettler and Maureen Coleman, postdoctoral associate Matthew Sullivan, and Jacob Jaffe of the Broad Institute. Additional authors are from Humboldt University, Harvard Medical School, and the University of Freiburg.

Funding for this research came from the Department of Energy, the Gordon and Betty Moore Foundation, and the National Science Foundation.