Thinking ahead: Bacteria anticipate coming changes in their environment

A new study by Princeton University researchers shows for the first time
that bacteria don't just react to changes in their surroundings -- they
anticipate and prepare for them. The findings, reported in the June 6 issue
of Science, challenge the prevailing notion that only organisms with complex
nervous systems have this ability.

"What we have found is the first evidence that bacteria can use sensed cues
from their environment to infer future events," said Saeed Tavazoie, an
associate professor of molecular biology, who conducted the study along with
graduate student Ilias Tagkopoulos and postdoctoral researcher Yir-Chung
Liu.

The research team, which included biologists and engineers, used lab
experiments to demonstrate this phenomenon in common bacteria. They also
turned to computer simulations to explain how a microbe species' internal
network of genes and proteins could evolve over time to produce such complex
behavior.

"The two lines of investigation came together nicely to show how simple
biochemical networks can perform sophisticated computational tasks," said
Tavazoie.

In addition to shedding light on deep questions in biology, the findings
could have many practical implications. They could help scientists
understand how bacteria mutate to develop resistance to antibiotics. They
also may help in developing specialized bacteria to perform useful tasks
such as cleaning up environmental contamination.

In one part of the study, the researchers studied the behavior of E. coli,
the ubiquitous bacterium that travels back and forth between the environment
and the gut of warm-blooded vertebrates. They wanted to explain a
long-standing question about the bug: How do its genes respond to the
temperature and oxygen changes that occur when the bacterium enters the gut?

The conventional answer is that it reacts to the change -- after sensing
it -- by switching from aerobic (oxygen) to anaerobic (oxygen-less)
respiration. If this were true, however, the organism would be at a
disadvantage during the time it needed to make the switch. "This kind of
reflexive response would not be optimal," Tavazoie said.

The researchers proposed a better strategy for the bug. During E. coli's
life cycle, oxygen level is not the only thing that changes -- it also
experiences a sharp rise in temperature when it enters an animal's mouth.
Could this sudden warmth cue the bacterium to prepare itself for the
subsequent lack of oxygen?

To test this idea, the researchers exposed a population of E. coli to
different temperatures and oxygen changes, and measured the gene responses
in each case. The results were striking: An increase in temperature had
nearly the same effect on the bacterium's genes as a decrease in oxygen
level. Indeed, upon transition to a higher temperature, many of the genes
essential for aerobic respiration were practically turned off.

To prove that this is not just genetic coincidence, the researchers then
grew the bacteria in a biologically flipped environment where oxygen levels
rose following an increase in temperature. Remarkably, within a few hundred
generations the bugs partially adapted to this new regime, and no longer
turned off the genes for aerobic respiration when the temperature rose.

"This reprogramming clearly indicates that shutting down aerobic respiration
following a temperature increase is not essential to E. coli's survival,"
said Tavazoie. "On the contrary, it appears that the bacterium has "learned"
this response by associating specific temperatures with specific oxygen
levels over the course of its evolution."

Lacking a brain or even a primitive nervous system, how is a single-celled
bacterium able to pull off this feat? While higher animals can learn new
behavior within a single lifetime, bacterial learning takes place over many
generations and on an evolutionary time scale, Tavazoie explained. To gain a
deeper understanding of this phenomenon, his team developed a virtual
microbial ecosystem, called "Evolution in Variable Environment." Each
microbe in this novel computational framework is represented as a network of
interacting genes and proteins. An evolving population of these virtual bugs
competes for limited resources within a changing environment, mimicking the
behavior of bacteria in the real world.

To implement this framework, the researchers had to deal with the sheer
scale and complexity of simulating any realistic biological system. They had
to keep track of hundreds of genes, proteins and other biological factors in
the microbial population, and observe them as they varied over millions of
time points. "Simulations at this scale and complexity would have been
impossible in the past," said Tagkopoulos. Even with the vast number
crunching power the supercomputers provided by the University's
computational science and engineering support group, their experiments took
nearly 18 months to run, said Tagkopoulos.

In this virtual world, microbes are more likely to survive if they conserve
energy by mostly turning off the biological processes that allow them to
eat. The challenge they face then is to anticipate the arrival of food and
turn up their metabolism just in time. To help them along, the researchers
gave the bugs cues before feeding them, but the cues had to appear in just
the right pattern to indicate that food was on its way.

"To predict mealtimes accurately, the microbes would have to solve logic
problems," said Tagkopoulos, a fifth-year graduate student in electrical
engineering and the principal architect of the Evolution in Variable
Environment framework.

And sure enough, after a few thousand generations, an ecologically fit
strain of microbe emerged which did exactly that. This happened for every
pattern of cues that the researchers tried. The feeding response of these
gastronomically savvy bugs peaked just when food was offered, said
Tagkopoulos.

When the researchers examined a number of fit virtual bugs, they could at
first make little sense out of them. "Their biochemical networks were filled
with seemingly unnecessary components," said Tagkopoulos. "That is not how
an engineer would design logic-solving networks." Pared down to their
essential elements, however, the networks revealed a simple and elegant
structure. The researchers could now trace the different sequences of gene
and protein interactions organisms used in order to respond to cues and
anticipate mealtimes. "It gave us insights into how simple organisms such as
bacteria can process information from the environment to anticipate future
events," said Tagkopoulos.

The researchers said that their findings open up many exciting avenues of
research. They are planning to use similar methods to study how bacteria
exchange genes with one another (horizontal gene transfer), how tissues and
organs develop (morphogenesis), how viral infections spread and other core
problems in biology.

"What is really exciting about our discovery is that it brings together and
establishes deep connections between the traditionally separate fields of
microbial ecology, network evolution and behavior," said Tavazoie.

Source: Princeton University
http://www.physorg.com/news132249060.html

Posted by
Robert Karl Stonjek