In politics, quorum is the number of people you need present to vote on legislation. It’s that minimum target you avoid by having politicians leave the state to stop ridiculous policies from being rammed through the system. It’s the number you aim for when bringing unwilling participants into the room kicking and screaming to further your own agenda.
In the microbial world, quorum is also an important number. It determines whether a colony of bacteria lay dormant to avoid the immune system or rouse the troops to begin an infection. It can change a benign group of microbes into a deadly biofilm. Or it can activate certain processes that are beneficial to the digestive system.
In politics, quorum is measured by taking roll call; by having those members present vocally indicate their proximity. In the microbial world, roll call is taken through chemistry. Bacteria secrete signaling chemicals that their brethren can detect. And once the concentration levels of those chemicals reach a certain tipping point, the bacteria start turning on or off different genes.
Helen Blackwell, a professor of chemistry at the University of Wisconsin, is messing with those signals. But rather than bringing in extra bacteria squirming and secreting, she’s blocking or imitating their “here” call.
A chemical signal works by a bacterium producing a protein that travels to its neighbor and binds in a specific receptor.Blackwell and her research group started changing key building blocks of the proteins one-by-one to find which were important to the signaling. They expected to simply block the signal, but instead, they found that they could completely flip the signal’s effect.
“It was surprising that making minor tweaks, very subtle changes, to the protein would convert a compound from an inhibitor to an activator, or turn an activator into an inhibitor,” said Blackwell. “That shows that small-molecule control of quorum sensing is very finely tuned, much more than we even expected.”
There are many potential applications to messing with bacterial communications signals, but perhaps the most interesting is medicine. As microbes evolve more defenses to our biggest and baddest antibiotics, it’s become more important to find other ways to thwart their infections.
Perhaps stopping their swarming signals is one way to go.
While current antibiotics are designed to kill microbes, the goal of quorum sensing would be to keep them “tame” and harmless, Blackwell says. “If these ‘on/off’ protein modifications are as important as we have found, they may help us design new compounds to inhibit quorum sensing and reduce the harm of bacterial infections, without causing the drug resistance that is producing so many problems today.”
The study, “Mutational Analysis of the Quorum-Sensing Receptor LasR Reveals Interactions that Govern Activation and Inhibition by Nonlactone Ligands,” was published by Blackwell with recent graduate students Joseph Gerdt and Christine McInnis.