Bacterium research could aid bioterror

WASHINGTON – Researchers in Germany reported Thursday they had altered the DNA of a disease-causing bacterium to enable it to infect a species it cannot normally sicken – a double-edged advance that experts said could deepen scientists’ understanding of human diseases but could also speed development of novel bioterror agents.

The change in infectiousness – the first of its kind ever engineered from scratch – poses no direct threat to human health, scientists said, because the microbe already causes a human disease: the food-borne illness called listeriosis.

The change allows that microbe to sicken mice, a species it has no natural capacity to infect.

Still, the work has biosecurity implications because it could, in theory, be applied in reverse, endowing a bacterium that causes a serious animal disease with an unprecedented ability to sicken people.

Several experts said they were disappointed that the report, in today’s issue of the journal Cell, does not mention those implications.

Also worrisome to some is that Cell’s editors did not seek outside advice as to whether publication of the study posed a security threat.

Aside from such worries, scientists said the new work marked a remarkable achievement in protein biophysics, a quickly maturing field that is revealing how proteins – the workhorses of living cells – interact with one another on the atomic scale.

Study leaders Wolf-Dieter Schubert and Andreas Lengeling, of the Helmholtz Centre for Infection Research in Braunschweig, knew that a particular protein on the surface of the bacterium IListeria monocytogenes/I was crucial to its ability to infect human intestinal cells.

The bacterium, which sometimes contaminates cheeses and other foods, causes a flu-like illness that kills about 500 Americans each year and is especially feared by pregnant women because it can kill a fetus.

Schubert had studied structural details of the protein on human intestinal cells that serve as a form-fitting landing pad, or receptor, for the bacterium and its surface protein during the infection process. And he knew the ways in which the mouse version of that protein differs slightly from the human version – which accounts for the microbe’s inability to infect mice.

Based on knowledge about how differently charged proteins interact with each other, the researchers predicted that the Listeria protein would settle reasonably well onto the mouse intestinal receptor if they could change just two of the bacterial protein’s amino acids, which are the building blocks of proteins.

They engineered Listeria’s DNA code so the microbe would start making surface proteins containing the two substitute amino acids. Those amino acids differ from the original ones by just eight atoms (plus a few hydrogen atoms attached to those eight).

But that minuscule change made a huge difference. When the researchers fed the altered bacteria to mice, the animals got sick with listeriosis.

“It is able to get into the bloodstream and reproducibly infect the mouse,” Schubert said.