Social Lives of Bacteria May Yield Benefits for Humans

By David Brown
Washington Post Staff Writer
Monday, July 28, 2008

There's strength in numbers. The best defense is a good offense. And it's okay if a few die as long as most survive.

People in the Middle Ages knew this, which is why they built castles, invented the crossbow and raised professional armies.

But the social organization and investment in technology that characterized the rise of modern civilization wasn't exactly a new idea. It turns out bacteria had been onto it for a couple of billion years.

Bacteria are without question among Earth's simplest forms of life. They are single-celled, have no nucleus, and multiply by simple cell division, not sexual reproduction. Nevertheless, research in recent years has revealed that they have complicated -- if entirely un-self-conscious -- social lives.

It's now clear that bacteria are capable of detecting their fellow bacteria, balancing personal and group needs, and, if necessary, laying down their lives for the common good.

The latest insight into this surprising and largely overlooked behavior came in a study published last week in the online Public Library of Science journal PLoS One. An international team of biologists reported that when some species of marine bacteria form immobile "biofilms" -- thereby becoming sitting ducks -- they begin to produce chemicals that are specifically toxic to the predators that show up to eat them.

"We found that biofilms are resistant whenever an attacker comes their way. The question is, how do they do it?" said Carsten Matz, a microbiologist at the Helmholtz Center for Infection Research in Germany who led the research team.

Biofilms consist of large collections of bacteria stuck together in a slimy "matrix" that the organisms themselves produce and secrete into the environment. They allow microbes to stay in a place that has lots of nutrients and thereby maximize their growth and cell division.

The existence of biofilms has been known for a long time. But what has become clear in recent years is that a bacterium in a biofilm behaves quite differently from the very same bacterium in the free-floating (or planktonic) state. The difference is in the organism's metabolism -- the making and breaking down of chemical compounds -- activities that require energy and are done only if there is a payoff.

A major insight was that biofilm-based metabolism is triggered by an event called "quorum sensing." Somehow, bacteria are able to detect the presence of other bacteria (usually of the same species) right around them. When the density gets high enough, the organisms switch into biofilm mode, producing and excreting the slime that then cements them together.

Quorum sensing depends on some sort of signaling among bacteria -- although because the organisms have no nervous systems, the signaling is clearly unintentional in the conventional sense.

For some biofilm-producing species, waste products appear to be the signal. When many bacteria are near one another, those substances rise to a concentration at which they are detectable by the individual organisms. They then trigger the metabolic changes. In other cases, though, there seem to be hormonelike compounds that exist for signaling purposes alone.

How quorum sensing works, and how it evolved, are big topics in biology that are only now being explored in earnest.

What the new study shows is that once it kicks in, quorum sensing stimulates the bacteria in biofilms to do more than make slime. They also make weapons.

Matz and his colleagues, several working at the Center for Marine Biofouling and Bio-Innovation at the University of New South Wales in Australia, studied 30 widely differing types of marine bacteria that were all readily eaten by protozoan predators when they were in their free-floating state. In their biofilm state, however, 22 were resistant to a surface-grazing flagellate, a single-celled organism called Rhynchomonas nasuta, and 17 caused the predator's numbers to decline drastically.

Further study revealed the bacteria were making a purple compound called violacein that was lethal to the predator. While they also made it when they were free-floating, production went way up in the biofilm state, triggered somehow by quorum sensing.

Numerous other bacterial species also made violacein, and other protozoa were susceptible to it. In one case, an amoeba dissolved within an hour of eating a single violacein-producing bacterium. This suggests, as other studies have, too, that something akin to altruism may have originated in single-cell organisms.

"Even though individual cells are ingested and do not survive to reproduce, the remaining [bacterial] population may benefit from reduced grazing pressure," the scientists wrote.

Biofilms are far more than curious biological communities; they have huge practical consequences, as well.

Bacteria in biofilms are often resistant to antibiotics that kill them easily when the organisms are free-floating. (By one estimate, 80 percent of chronic bacterial infections involve biofilms.) Finding ways to block their formation -- or to soften them up so that predators like white blood cells of the immune system can move in more easily -- is a major area of research.

The toxic effects of compounds such as violacein also suggest that biofilms may be good places to look for new drugs.

Malaria, Chagas' disease and sleeping sickness are just a few of the many human diseases caused by protozoa. There is also reason to think that some biofilm-forming bacteria may make substances that suppress other bacteria -- and therefore could be possible antibiotics.

Matz and his colleagues isolated 14 toxins from biofilms in their recent experiments. They are now exploring their function with the help of a pharmaceutical company.


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