Scientists have long believed that a certain biochemical pathway involved in the folding and delivery of proteins to cell membranes is essential for survival. However, researchers at the University of Florida, Gainesville, have discovered that Streptococcus mutans, the caries-causing organism that thrives in human mouths, can survive without it.
The findings, reported in the Nov. 29 issue of Proceedings of the National Academy of Sciences, have rocked the cellular biology scientific community, which has long considered the pathway to be crucial.
"We were met with skepticism ...because the dogma was that this biochemical pathway is key for all living cells," said study investigator Jeannine Brady, PhD, an associate professor of oral biology at the University of Florida College of Dentistry. "As far as we know, this is the first example of any bacteria that can cope without this pathway; all of the existing literature indicated it is vital."
The signal recognition particle (SRP) pathway is a primary mechanism by which proteins are delivered 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 its natural environment of the human mouth, S. mutans typically goes on the attack. When sugary foods are eaten, the S. mutans population explodes, excreting lactic acid as it digests sugar. The acid prevents helpful bacteria from thriving and demineralizes tooth enamel, causing caries.
In an effort to understand how best to combat the caries causing properties of S. mutans, Dr. Brady and the other researchers set out to learn how the organism was able to survive its own acid. They 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, PhD, 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 that a backup pathway was in place.
However, the altered bacteria could not contend with sudden environmental change. When artificially shocked with acid to a pH below that at which 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, Dr. Hasona said.
The research team surmised that two other molecules—YidC1 and YidC2—might be acting as alternate routes for protein delivery in the absence of the SRP pathway. They tested their hypothesis and found that S. mutans could continue to function in nonstress conditions without the SRP and YidC1 genes, but not without the YidC2 and SRP simultaneously.
"The fact that the bacteria could survive without the SRP pathway was the most striking finding for scientists in the membrane protein insertion field," said Ross E. Dalbey, PhD, a professor of chemistry at The Ohio State University, Columbus. "The big question now is discovering how these proteins are targeted in the absence of the SRP pathway, and I think that will be an important area of future research."
