Bacteria locked in long term solitary confinement change their behavior in strange ways, scientists find, in research that could help explain how infections and cancer spread.
Humans in solitary confinement can go crazy, talking to themselves and trying to break free. Now scientists from New Mexico and New Hampshire are reporting that bacteria locked in solitary confinement know they are locked up, talk to themselves, and try to break free of their imprisonment.
The research could have important health implications, from how an individual bacterium can trigger full-blown infections to how a single human cancer cell can metastasize into a deadly tumor.
"There are many real-world situations where bacteria find themselves alone," said Jeff Brinker, a scientist at the University of New Mexico and co-author of a recent paper in the journal Nature Chemical Biology. "When the bacteria are confined they turn on these virulence pathways," causing infections.
A human locked up in solitary confinement can see the walls around them, touch their rough surfaces, hear their pleas and curses echoing around the cell. Bacteria lack these senses, but they do have excellent noses. They smell the walls around them, using a chemical process known as quorum sensing.
Quorum sensing is how bacteria communicate with each other, and with the world around them. Bacteria send out specific chemicals, often called autoinducers, that diffuse away, their concentration decreasing the farther away the chemical travels. Low levels of autoinducers usually means that a bacterium is alone. High levels of autoinducers means there are many bacteria.
Once the signal reaches a certain threshold, or quorum, the bacteria change their behavior, turning some genes on, turning other genes off. The bacteria become an organized pack, known as a biofilm, instead of lone wolves. In a biofilm, certain bacteria are responsible for protection, others for food, and still others for replication. A biofilm can be anything from the brown scum on river rocks to the yellow mucus hacked up during a lung infection.
But what happens when there are high levels of autoinducers but only one bacterium?
Until now the technology to create glass cages 20 micrometers wide to hold bacteria three to four micrometers long didn't exist. Now nanotechnology has advanced to the point where scientists can trap these tiny organisms in glass cages and watch the imprisoned bacteria, in this case Staphylococcus aureus, talk to themselves.
The conversations are angry. The bacteria know their messages, or quorum sensing molecules, are going nowhere. If the chemicals can't move anywhere then neither can much larger bacteria. If bacteria can't move it means they are trapped, either inside a tissue or inside another cell, usually a macrophage, that is attempting to destroy the invading cell.
Either way, bacteria needs to get out, and they activate genes that will help them escape. The Staph produces lysosomes, chemical bombs that eat away at whatever they touch, and releases them into the environment around it. Since the cage is glass, the lysosomes are ineffective, but the bacteria continue to pound the walls with them.
A bacterial change like this isn't supposed to happen. A quorum of chemicals from dozens, hundreds of bacteria packed close together is supposedly the only way for a bacteria to alter its gene expression.
"This is really a way for cells to fight back, to adapt to any condition a cell finds itself in," said Brinker. "All that's needed is a quorum of one."
Staph bacteria can cause serious, life-threatening infections in humans. The new research could eventually have important applications in finding ways to stop individual Staph cells, and other pathogens, from becoming full-blown infections. Equally important, however, is the new research's implications for cancer, says Brinker and other scientists, including Carrie Rinker-Schaeffer, a scientist at the University of Chicago.
Just like invading Staph, a cancer cell that breaks off from the main tumor can find itself trapped, isolated, and trying to figure out where it is using chemical signals. Scientists don't know which chemicals metastatic cancer cells use, but they expect to start finding them soon.
Whether the cells involved are invading pathogens or metastatic cancer cells, "these are some very complicated questions," said Rinker-Schaeffer. "But if you take the process of bacterial infection and metastatic cancer colonization and line them up, the similarities are amazing."