Mob Mentality: ​Bacteria send signals before massing for an attack. Helen Blackwell has discovered how to listen in, and block deadly cells’​ ability to swarm.

for Sift & Winnow, first published here

When Helen Blackwell describes how disease-causing bacteria become virulent, it’s hard not to imagine the little buggers whistling to each other in a dark alley, like bad guys getting ready to rumble.

Blackwell, a professor of chemistry, studies the role chemical signals play in helping bacteria communicate and act as a group. Through a process known as quorum sensing, bacteria are able to detect and count others of their kind nearby. And when dangerous bacteria decide there are enough of them present in a particular environment to mount an assault, they band together and attack their host. “It’s like a mob mentality,” Blackwell says. “Bacteria wait until there are a lot of them, and then they say, ‘OK. I’m going to invade.’”

Learning about deadly bacterial cells’ ability to suddenly swarm or form slimy protective coatings, known as biofilms, around themselves “blew my mind,” Blackwell recalls. But then she began to wonder if she could change how bacteria behave.

As an organic chemist who earned her doctorate at the California Institute of Technology, she already knew how to make synthetic molecules. So she decided to start experimenting with the structure of molecules to see if her own compounds, added to bacterial cells, could change how the bacteria are able to count each other. Working closely with a team of dedicated graduate students in her lab, she has developed a range of new compounds that interrupt quorum sensing communication — effectively blocking deadly bacterial cells’ ability to swarm and form biofilms.

Known as quorum sensing inhibitors, or QSIs, Blackwell’s compounds show tremendous potential for both treating and preventing the spread of serious bacterial diseases, including staph infections and pneumonia. Unlike traditional antimicrobial drugs, which simply kill bacteria (even the good ones that live in our gut) and fuel antibiotic resistance, the chemical agents Blackwell has developed target only the most deleterious behaviors of dangerous bacteria. This keeps them from infecting their host, yet allows them to live and thus reduce the resistance threat.

Scientists still have plenty to learn about bacteria and quorum sensing before chemicals like hers are ready for the market, Blackwell notes. But there is solid and growing evidence suggesting that QSIs could be useful in a range of clinical and industrial settings. For example, QSIs could be incorporated into polymer coatings designed to inhibit bacterial growth on medical equipment, including replacement joints, or wound dressings.

Another exciting possibility is that QSIs could be used to “rescue” (as drug researchers phrase it) certain antibiotics that are rarely used because they’re so highly toxic. By giving patients with dangerous infections QSI-based medications that would block bacterial communication, it might be possible to reduce bacterial levels so that now a lower, non-toxic dosage of the antibiotic could clear the infection. Blackwell also hypothesizes that QSI-based drugs could lower bacterial loads to an extent that the patient’s immune system may be able to clear the bug on its own, avoiding the need for antibiotics altogether. Research to test these hypotheses, she notes, is ongoing.

A fellow of the American Association for the Advancement of Science, Blackwell has received numerous prestigious awards for both research and teaching, including the American Chemical Society Arthur C. Cope Scholar Award and an Alfred P. Sloan Research Fellowship, as well as the UW-Madison Chancellor’s Distinguished Teaching Award.

Lately, Blackwell says, her mind has been blown again as researchers have learned much more about how different bacteria work together, for better and worse, in different communities, including the human microbiome. But unlike researchers who are just focused on one bug, she’s already deep into exploring how chemistry can be used to start and reroute a wide range of bacterial conversations between the many different bacteria that live in the environments that surround us, and within us.

“Thinking about how bacteria work together collectively, as opposed to just as individuals, makes science harder to do,” Blackwell says with a smile. “But in the end, the answer will be so much more interesting.”