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NIH-funded Research Aims to Silence Bacteria

By: Kathleen Tuck   Published 1:07 pm / June 13, 2016

Rajesh Nagarajan with follow researchers in the lab.

Communication is an essential survival skill among all species, even the microscopic variety. But while humans generally use words and gestures to express needs, and animals screech, bark and howl, bacteria communicate using chemical molecules.

Understanding that chemical language is the goal of Boise State biochemist Rajesh Nagarajan, who recently received a $395,813, three-year grant from the National Institutes of Health to solve the problem.

Specifically, Nagarajan will look at how bacteria make the signal molecules to communicate with their neighbors. This communication happens only when bacteria need it in order to form a critical mass and attack, and different bacteria use different enzymes to, in essence, speak a specific language understood only by other targeted bacteria.

Cartoon explaining how quorum sensing worksTo do this, they use quorum sensing, or the ability to sense how many similar bacteria are in the immediate vicinity. To facilitate quorum sensing, each bacterium uses a specific enzyme to create a unique signaling molecule, diffuse it into the surrounding environment, and ultimately count these signals to determine if the local bacterial population has reached a “quorum” necessary to trigger virulent behavior. This step ensures the timing is just right for the bacteria to go on an offensive/attack mode.

“Somehow each bacterium precisely knows which signal molecules to make,” Nagarajan said. “That’s important because making signal molecules that don’t communicate with the correct species is a waste of energy and helps the competition.”

Rajesh Nagarajan, NIH Grant, Allison Corona photo

Nagarajan wants to find out how enzymes know to make that one specific signal molecule out of many choices available so he can “crack the language” of enzymes.

Keep in mind that the human body harbors several trillion bacteria cells. “When pathogenic bacteria communicate with each other, bad stuff happens,” Nagarajan said. Currently, the only way to combat their harmful effects is the use of antibiotics, which are becoming less effective as bacteria evolve and become resistant.

A better route would be to figure out how they communicate and then develop inhibitors to essentially jam their communication signals. Because the bacteria aren’t under attack, they don’t develop resistance and, theoretically, can be eradicated with a low dose of antibiotics.

The signal synthesis enzyme uses two substrates to construct signal molecules: acyl carrier proteins (Acyl-ACP) and S-Adenosyl-L-Methionine (SAM). Acyl-ACP is made through the biosynthesis of fatty acids and the body creates more than one type at a time. Somehow, the enzyme has to figure out which Acyl-ACP to select in order to “tune in” to the chatter going on between bacteria.

“Quorum sensing signal synthesis enzymes are remarkably efficient in amplifying signal over noise during microbial communication,” Nagarajan said. “But how they do it is a million-dollar question.”

He currently is teaming up with both graduate and undergraduate students at Boise State to understand the molecular basis of this mystery. Results could have a significant impact on how we treat infectious disease.