Study Questions Need For Biochemical Pathway

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Leave it to the bacteria that cause tooth decay to be able to live without something all cells were thought to require.

Scientists have long believed a certain biochemical pathway involved in the folding and delivery of proteins to cell membranes is essential for survival. Now researchers have discovered that Streptococcus mutans, the decay-causing organism that thrives in many a mouth, can do just fine without it.

The findings, reported in the December Proceedings of the National Academy of Sciences, have rocked the cellular biology scientific community, which has long considered the pathway to be crucial. The report may also explain why strains of the bacteria can survive in the harsh acidic environment they create in the mouth.

“We were met with skepticism … because the dogma was that this biochemical pathway is key for all living cells,” said study investigator Jeannine Brady, an associate professor of oral biology at the UF College of Dentistry. “As far as we know, this is the first example of any bacteria that can cope without this pathway.”

The signal recognition particle, or SRP, pathway is a primary mechanism by which proteins are chaperoned from cellular assembly lines, where they are made, to the protective outer surface of the cells, where they are inserted. Without a steady infusion of proteins, the membrane weakens and the cell — in this case, a bacterium — becomes unable to protect itself from harsh environmental conditions.

In the human mouth, its natural environment, it is typically S. mutans that goes on the attack. When sugary foods are eaten, the S. mutans population explodes, excreting lactic acid as it digests sugar. The acid makes life difficult for other helpful bacteria and demineralizes tooth enamel, causing decay.

In an effort to understand how best to combat the tooth-decaying properties of S. mutans, Brady and her team set out to learn how the organism was able to survive its own acid. The researchers tinkered with systematically turning off several genes, individually and in combination, to see how the bacteria responded.

“We found S. mutans can survive, with normal growth, without the SRP pathway,” said Adnan Hasona, a research assistant professor of oral biology and the study’s lead author.

The bacteria altered to lack SRP components were able to adapt and survive gradual increases in acid resulting from their own metabolism, suggesting a backup pathway was in place.

But, like goldfish dropped in new water, the altered bacteria could not contend with sudden environmental change. When artificially shocked with acid to a pH below that where tooth demineralization begins, the altered bacteria became sick and unable to grow. Shocking the bacteria with other environmental stressors, such as high salt levels or the presence of hydrogen peroxide, also caused them to weaken, Hasona said.

“So, at least in this organism, we learned the SRP pathway seems to enable it to respond rapidly to environmental stress, but it was not at all necessary for the organism’s viability during non-stress conditions,” Brady said.

“Really, we started with a very basic question related primarily to S. mutans, ‘how does this bacteria tolerate acid?’” said Brady. “Asking that question has opened the door much more widely to learning things that are more fundamental about how living organisms insert proteins and how membrane function is determined by proteins.

The study was funded by the National Institute of Dental and Craniofacial Research.

Jeannine Brady, jbrady@dental.ufl.edu
Lindy McCollum-Brounley