Protecting the Unborn from F. Nucleatum

does a harmless plaque isolate become a rampaging poison that can cause

fetal death — and, can it be stopped? Yiping Han is newly armed with

nearly $2 million in research money that will be used to answer these

questions and neutralize the threat of Fuscobacterium nucleatum,

a bacterium unremarkable inside the mother’s mouth that can become

lethal once it breaches the immune-free environment inside the placenta.

Han,

associate professor at the Case Western Reserve University School of

Dental Medicine, hopes to fashion a roadblock of sorts that will stymie

the potentially deadly organism before it reaches an unborn child. She

has received a five-year, $1.85 million grant from the National

Institute of Dental and Craniofacial Research (NIDCR) at the National

Institutes of Health to back her work.

Finding a crucial weakness

In earlier work Han discovered an adhesin protein molecule called FadA in the genes of F. nucleatum.

This adhesin, or binding agent, on the bacteria allows them to connect

with receptors on epithelial cells in the mouth, and later the

endothelial cells of the placenta.

In tests, bacteria without

FadA had less binding capability compared to those with the adhesin.

Han and a team of researchers report on this finding in the July issue

of the journal Infection and Immunity.

“In some way,

the receptors on the host cell activate a signal that puts into action

a cascade of processes that allow the bacteria to penetrate the

epithelial and endothelial linings and then colonize,” Han explains.

“With

this new grant, we will be able to continue a functional analysis of

FadA,” Han says. Her research group will look not only at the binding

agent but the receptors on the host epithelial and endothelial cells

that promote the binding of the oral bacteria.

The best offense is a good defense.

“We

want to block the bacteria before it can do any damage,” Han says.

“It’s an upstream approach to go back to where the whole process begins

and stop it from starting its destruction.”

Once it leaves the

mouth, the invasion of the bacteria through the placenta allows the

bacteria to multiple rapidly in the immune-free environment that

protects the fetus from being rejected by the mother’s body. The rapid

bacterial growth causes the placenta to become inflamed. In turn, the

inflammation can trigger preterm birth and fetal death.

According

to Han this research into the mechanisms of bacterial transport not

only has potential to prevent preterm and stillborn births, it may also

have implications in preventing periodontal disease.