NIH awards IU biologist $1.89 million to 'disarm' deadly bacteria

Research on 'cellular chatter' in bacteria could lead to infectious disease treatments

The National Institutes of Health has awarded a biologist at Indiana University Bloomington a grant to investigate the disruption of "cellular chatter" in bacteria that cause diseases such as tuberculosis and cholera.

Julia C. van Kessel, assistant professor in the IU Bloomington College of Arts and Sciences' Department of Biology, will receive $1.89 million from the National Institutes of Health's MIRA Award program to study "quorum sensing," a form of cellular communication that helps microorganisms detect whether their population numbers are large enough to perform an action. These actions could be as benign as emitting a faint glow or as dangerous as launching a disease-causing attack against the body.

"The goal of our research is to understand how cell-cell communication controls the ways bacteria cause disease," said van Kessel, who joined the IU faculty in 2016. "The larger goal is the development of drugs that target the quorum-sensing pathway. When bacteria can't use quorum sensing to count their numbers, they don't know when to launch their 'attack' and can't cause disease."

Current drugs used to treat infection work by preventing bacterial cell growth, causing the microorganisms to die or develop resistance to the drug. Drug-resistance bacteria are a growing public health crisis that disproportionally affect the elderly and infirm. Drugs that prevent quorum sensing could cause less drug-resistant bacteria by preventing disease without killing the microorganism, allowing the body's immune system to clear the infection.

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Scientists in van Kessel's lab can "paint" with the bioluminescent bacteria used to study quorum sensing. Quorum sensing controls expression of the genes in the bacteria that enable the cells to "glow in the dark" after reaching high numbers. Image courtesy of the van Kessel Lab

"It's like taking the weapons away from the army but not killing the soldiers," van Kessel said. "Bacterial 'disarmament' is a more effective strategy to stop the war with much less damage."

Van Kessel's research will focus on several bacteria in the Vibrio genus -- Vibrio cholerae, Vibrio vulnificus and Vibrio parahaemolyticus -- which cause illnesses such as cholera as well as severe vomiting, fevers and skin infections. In the United States, V. vulnificus and V. parahaemolyticus are estimated to sicken about 80,000 people per year and cause about 100 deaths. V. vulnificus can also cause a rare but serious infection known as septicemia that kills about half of people affected. V. cholera causes cholera, which is rare in the U.S. but common in developing areas of the world.

Vibrio infections are most common in regions with inadequate water treatment and sanitation, or areas recovering from natural disasters. A severe outbreak of cholera followed the 2010 earthquake in Haiti, for example.

Another goal of van Kessel's research will be studying quorum sensing in a second type of bacteria called Mycobacteria. Among the species of Mycobacteria is one that causes tuberculosis, which is estimated to infect about one-third of the world's population, causing about 2 million deaths each year. Other species of the bacteria cause diseases such as leprosy, skin infections and lung diseases.

Specifically, van Kessel's work will focus on LuxR/HapR proteins, which her research has previously identified as playing a central role in quorum sensing by controlling hundreds of genes that allow bacteria to behave and "cooperate" as a group. This includes actions such as toxin secretion, biofilm formation and bioluminescence.

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The larger goal of research on quorum sensing is preventing the spread of infection from bacteria in the genus Vibrio, which can cause cholera, as well as vibriosis (severe vomiting, fevers and skin rashes). Image courtesy of the Centers for Disease Control and Prevention

The majority of the research into quorum sensing will occur in a less infectious form of the bacteria, a bioluminescent strain of Vibrios whose cellular mechanisms behave similarly to infectious types of the bacteria but without risk to scientists in the lab, van Kessel said.

The use of this bacterial species as a model system for quorum sensing traces back to quorum sensing's discovery over 40 years ago by scientists who found that bioluminescent Vibrios only glowed after reaching large enough numbers. By observing this behavior, these researchers found that certain proteins in the bacteria produced molecules used to communicate between cells.

"If we can learn enough about how LuxR/HapR function in cell-cell communication, then we can develop drugs that target these proteins to block their activity," van Kessel said. "Ultimately, if the cells cannot communicate to change their gene expression, they can't launch their 'attack' on the body."

MIRA, or Maximizing Investigators' Research Award, grants are part of the National Institute of General Medical Sciences' Outstanding Investigator Award Program. The awards are granted to investigators with outstanding records of productivity and innovation. Support from the NIH award officially began Sept. 18.