Miller to speak on how salmonella avoid destruction

Sam Miller

UW School of Medicine researchers have unveiled the elegant molecular detail of the surface modification that Salmonellae bacteria use to slip past our early immune responses.

Salmonellae cause systemic typhoid and gastroenteritis (diarrheal illness). The breakthrough may lead to the development of new antibiotics and vaccines to fight these infections.

“Right now we’re in the midst of a world-wide problem of resistance to antibiotics and we need new classes of antibiotics,” said microbiologist Dr. Samuel I. Miller, who recently published the results in the October 16 issue of Cell.

“We have also discovered that this surface modification is a more general phenomenon used by a wide variety of bacteria,” he said.

Three years ago, Miller, a professor of medicine and microbiology, discovered that bacteria sense their environment and modify the molecular structure of their outer membrane to cloak themselves from our innate defenses.

Now, he and his colleagues have elucidated the molecular detail of the organism’s cloaking mechanism and can begin to develop drugs to inhibit the process.

Miller will discuss these advances in a Science in Medicine Lecture from noon to 1 p.m. on Friday, Nov. 20, in room D-209 of the Health Sciences Center. Miller’s talk is titled, “Bacterial Evasion of Host Innate Defenses.”

“Our work has shown that the organism can modify the lipid A component of lipopolysacharide (LPS) and that this modification takes place when the host is infected,” Miller said.

LPS, a glycolipid, is the major component on the outer surface of Salmonellae bacteria. Immune system cells in our bodies sense lipid A on the outside of a bacteria and trigger the release of antimicrobial peptides that would normally break through the cell surface and dissolve the invader.

When a bacterium senses the host environment, it begins a chemical restructuring that results in stronger lipid A molecular bonds on its surface. In this way, bacteria slip past the front line of our defenses.

“The organism is promoting its survival by resisting antimicrobial peptides,” said Miller.

If researchers can develop drugs to stop the organism from restructuring lipid A molecules, they may be able to treat patients whose immune systems have been compromised. Such drugs could boost the immune systems of AIDS or cancer patients, for instance.

Miller received an M.D. from Baylor College of Medicine in Houston in 1979. He came to the UW from Harvard Medical School and Massachusetts General Hospital in 1985 as an associate professor of medicine and microbiology. He became a full professor this year. ¶

Will Morton