A team of six Yale scientists have discovered how to manipulate the cell wall of a bacterium, allowing for the addition of small particles to its exterior — essentially tricking the bacteria into becoming a target for the body’s immune system.
Led by assistant chemistry professor David Spiegel GRD ’04 MED ’04, the researchers “tricked” the bacterium Staphylococcus aureus — which is responsible for the sometimes-fatal infection, Methicillin-Resistant Staphylococcus Aureus (MRSA) — into accepting small foreign molecules into its cell wall. Published in the scientific journal ACS Chemical Biology on October 5, this study is the first to successfully integrate synthetic substances into gram-positive bacteria and this achievement could have a far-reaching impact on the detection and treatment of other bacterial diseases, Spiegel said.
The six researchers focused their research on the enzyme sortase A, a catalytic protein which is naturally found in the Staphylococcus aureus bacterium and whose role is to attach proteins to the cell wall of the bacterium. Spiegel said the research team created biosynthetic materials that the enzyme would recognize.
“The normal job of the enzyme is to look for proteins that carry a certain composition,” he explained.
Sortase A succeeded in attaching common biochemical markers to the cell wall of Staphylococcus aureus, Spiegel said. The incorporation of foreign markers into a cell wall can, in some cases, provoke the response of a person’s immune system and the recruitment of antibodies, he said.
Spiegel explained that the antibodies “excite” the immune system, which allows the body to more effectively combat disease by increasing the activity of its immune cells.
”There has been great success in making molecules that recruit antibodies to the surface of HIV and prostate cancer,” he said. “I’m excited that this can occur in bacteria as well.”
Spiegel said he believes that an analogous method could be used to attack diseases like MRSA.
MRSA is a bacterial infection that causes painful and swollen areas on a person’s skin and which can have more serious symptoms of fatigue, shortness of breath and chest pains, according to Google Health. The National Institutes of Health website said that there are two main types of MRSA — one is found in hospitals, while the other is prevalent among people who have high rates of close skin-to-skin contact with others, as occurs in sports like wrestling.
According the Center for Disease Control’s website, more than 19,000 people died of MRSA — which is resistant to the most commonly used antibiotics in hospitals — during 2005. 84 percent of fatal MRSA cases were contracted in a hospital setting, the website said.
Although his broader interest is chemistry, Spiegel said he was drawn to this research because of his medical background; he obtained both a medical and a doctorate degree during his time at Yale. Spiegel also said he was inspired by the idea that these “small molecules” could open up a new paradigm of research.
The study is fundamentally different from previous research, Spiegel explained, because his methods utilize the bacteria’s own metabolic processes. In other words, the bacteria itself incorporates the molecule into its cell wall without the prodding of scientists. This method would allow the same attachment to occur within the human body, adding to the practical applications of this research.
The research also focuses on the manipulation of the cell wall of a bacterium in a way that prior experiments have not done, Robert Clubb, a biochemistry professor at University of California, Los Angeles, said. He said that other experiments have targeted their research towards different parts of the microorganism.
These experiments on the manipulation of a cell’s structure could aid in tracing the bacterium throughout the body, said Clubb. They could even have applications in the detection of toxic compounds, he added.
These advances are particularly important given the prevalence of infections like MRSA in the general population.
But, the results of the study do not stop with Staphylococcus aureus. Diseases caused by bacteria with a similar structure and nature could also reap the benefits, said Spiegel.
“In fact, we have tested similar bacteria, on which this method has worked as well, if not better,” he added.
However, Spiegel said he could not disclose the exact bacteria because this information is part of his unpublished research on other bacterial diseases.
Spiegel’s research was funded by the National Institutes of Health Director’s New Innovator Award program and a Bill and Melinda Gates Grand Challenges Explorations Award.
Correction: October 13, 2010
An earlier version of this article incorrectly spelled “Staphylococcus aureus.”