Scientists have sequenced thousands of bacterial genomes, and even demonstrated that it is possible to sequence whole genomes of emerging pathogens within days. But they are now beginning to uncover another layer of information that appears to be critical for understanding—and maybe controlling—bacterial pathogenicity: epigenetic modifications.
The ability to detect epigenetic additions to bacterial genomes is relatively new, supported by a sequencing machine from Pacific Biosciences (PacBio) that has been available commercially for just 2 years and supportive software released less than 7 months ago. But already, the technique is making waves in microbiology.
In the midst of the 2011 Escherichia coli outbreak in Germany that killed more than 50 people, Eric Schadt, director of the Icahn Institute for Genomics and Multiscale Biology at the School of Medicine at Mount Sinai and former chief scientific officer of PacBio, rapidly sequenced the dangerous bacteria using the PacBio sequencer. His team—along with other groups that were also sequencing the bacterium— discovered that it had acquired a Shiga toxin from a phage that could mostly explain the microbe’s increased virulence. But at first, they did not look at the methylation information. “We didn’t appreciate at the time that the methylation may be associated with the virulence!” Schadt wrote in an email to The Scientist.
Upon revisiting the data—and applying the new software—Schadt and colleagues discovered that along with the Shiga toxin, this particular E. coli had also adopted a methylase from the same phage. This methylation-laying enzyme resulted in a complete epigenetic makeover, the team learned. The group is still working on characterizing the effects of these epigenetic modifications, but Schadt said that the various pathways that were upregulated and downregulated in the bacterium, including changes in swarming and growth patterns, could have contributed to making it more virulent.
The technology is transforming the study of bacterial genome modification, said Richard Roberts, chief scientific officer at New England Biolabs, who started collaborating with PacBio to investigate bacterial epigenetics in 2010. In addition to simply mapping the epigenomes of hundreds of bacteria species, including emerging pathogens, Roberts is adding to his library of knowledge on how bacteria use methylation to protect their genomes from the restriction enzymes they release to cut up invading viral DNA. Other researchers are working on understanding the role of methylation in the cell cycle.
“It’s like you’ve been in a closed room for a long time, and you open the window and look out,” said Roberts. “And there’s a whole lot of stuff out there, and you don’t know where to look.”