Genetically engineered bacteria can commit suicide for good of
26 November 2012
Scientists at EMBO in Heidelberg have engineered bacteria that
are capable of sacrificing themselves in certain conditions where it
benefits the bacterial population. These 'altruistically inclined'
bacteria, which are described online in the journal Molecular
Systems Biology, can be used to demonstrate the conditions where
programmed cell death becomes a distinct advantage for the survival of
the bacterial population.
“We have used a synthetic biology approach to explicitly measure
and test the adaptive advantage of programmed bacterial cell death
in Escherichia coli,” said Lingchong You, senior author of
the study and an associate professor at the Department of Biomedical
Engineering, Duke University, and the Duke Institute for Genome
Sciences & Policy.
“The system is tunable which means that the extent of altruistic
death in the bacterial population can be increased. We are therefore
able to control the extent of programmed cell death as well as test
the benefits of altruistic death under different conditions.”
Scientists have known for some time that programmed cell death
can be linked to the response of bacteria to stressful conditions,
for example starvation of amino acids or the presence of competitor
molecules. However, it is not clear why cells should choose to die
under such conditions since it gives them no immediate advantages.
Some researchers have suggested that programmed cell death allows
cells to provide benefits to their survivors but until now it has
been difficult to test this directly in experiments.
The researchers used synthetic biology procedures to engineer
Escherichia coli in such a way that the bacterial cells are
capable of suicidal behaviour and promoting the good of the
bacterial population. To do so they introduced a gene circuit, which
consists of two modules, into the bacteria.
If the “suicide module” is active it leads to the rupture and
death of some bacterial cells when they are challenged with the
antibiotic 6-aminopenicillanic acid. If the “public good” module is
expressed, a modified form of the enzyme beta-lactamase is produced,
which protects surviving cells from rupture or lysis by breaking
down the antibiotic. This protection only occurs when the enzyme is
released from inside the bacterial cells that make the ultimate
sacrifice and die after rupture.
“Our results clearly demonstrate that it is possible to have
conditions where the death of some bacteria confers an advantage for
the overall population of bacteria,” remarked You. “The optimal
death rate for the bacterial population emerges after sufficient
time has passed and is clearly visible in our system.”
The scientists were also able to provide a possible explanation
for the “Eagle effect”, an unexpected phenomenon where bacteria
appear to grow better when treated with higher antibiotic
concentrations. “Overall our results fill in a conceptual gap in
understanding the evolutionary dynamics of programmed bacterial
death during stress and have implications for designing intervention
strategies for effective treatment of bacterial infections with
antibiotics,” concluded You.
The research is published as: Yu Tanouchi, Anand Pai, Nicolas E
Buchler, Lingchong You. Programming stress. Nature.