Bacteria may seem like exceedingly simple and lonely organisms, but more and more evidence shows they can communicate, act collectively, and respond to their changing environments. At the 2016 ASCB Annual Meeting “Cellular Communities” Symposium, Bonnie Bassler, professor at Princeton University and Howard Hughes Medical Institute (HHMI) investigator, and Dianne Newman, professor at the California Technology Institute and HHMI investigator, will be share their latest research on bacterial communities. Jürgen Knoblich, professor at the Institute of Molecular Biotechnology in Vienna, Austria, will also speak in the Symposium, about his work in stem cell communities.
Newman studies how bacteria survive in stationary phase, or when they’re not rapidly doubling their population. “Less attention is paid to this phase of bacterial growth at the molecular level, historically. But in nature this phase of growth is much more representative of how bacteria actually live,” Newman said. Her lab has been focused on investigating secondary metabolites, small molecules that are products of metabolism, made by bacteria under these conditions. “We’ve been studying their biology, what they do for the organisms that produce them… We’ve found [secondary metabolites] have many primary functions for survival, including contributing to biofilm development as signaling molecules and facilitating energy generation and iron acquisition,” Newman said.
The Newman lab’s latest studies have focused on Pseudomonas aeruginosa. “You can find it everywhere, in many different habitats. Where it’s become notorious is in the lungs of cystic fibrosis patients. It’s well adapted to surviving in the lung as it fills with mucous,” she said. While investigating a class of secondary metabolites made by Pseudomonas called phenazines Newman and colleagues recently discovered that “an enzyme [that degrades a particular phenazine] actually inhibits biofilm development. We weren’t expecting it to have the impact that it did. We are excited about potential therapeutic possibilities,” she said.
“Our studies have just begun to scratch the surface about what these metabolites are doing. There is so much in the microbial word that hasn’t been looked at, because classical reductionist laboratory studies were not designed with high fidelity to nature,” Newman said. Not that these past studies weren’t tremendously valuable, Newman and Bassler pointed out. “The reductionist approaches [of the past] have positioned us to learn something meaningful when we take on new challenges outside the flask,” Bassler said.
Bassler researches “how bacteria communicate, count their numbers, and control their collective behaviors, and that’s called quorum sensing,” she said. Bassler first learned about bacterial communication at a conference where Mike Silverman “showed that this obscure glow-in-the dark marine bacteria made light in unison,” she said. Bassler was captivated by the possibility and went on to do a postdoc in his lab, and she has been studying bacterial communication since.
“Bacteria use multiple molecules to talk. For example, there will be a molecule that is exquisitely species specific, that’s how bacteria count their kin, another molecule says ‘I’m your cousin,’ and another is generic for all bacteria. The bacteria interpret these and they do different things depending whether they and their kin are in the majority, or whether other bacteria are in the majority,” Bassler explained. And there are plenty of these types of molecules waiting to be identified, she said.
The Bassler lab recently discovered a molecule made by bacteria in the human microbiome that helps us fight pathogens. “In the microbiome, bacteria live on all kinds of substrates that we feed them, but they also live on mucin, the mucus that covers the intestinal lining.…[T]he microbiome digests that and they use the threonine from it, and make a molecule, an autoinducer, that pathogens interpret and disperse… it reduces infectivity,” Bassler said.
Bassler, too, is exploring the therapeutic potential of her work. “My lab is making synthetic molecules that are able to turn on or off quorum sensing on demand. These molecules are being developed into medicines, applications for industry, coatings for surfaces, and infection- resistant materials,” she said. But Bassler warned that clinical applications are a ways off. “The molecules exist and they work in a test tube, but we have to figure out how to deploy them safely and smartly.”
Both Bassler and Newman are in awe of their micro subjects, and excited by the possibilities they present. Said Newman, “there is so much basic science to discover in understanding how bacteria survive.” “Bacteria are ingenious, it’s a privilege to get to figure this stuff out. We have to have humility; bacteria have had 4 billion years to establish themselves. They’re so sophisticated, and we assume they’re so simple, and they’re not,” Bassler says.