Duke Scientists Deconstruct Process of Bacterial Division
DURHAM, N.C. -- Duke University researchers have made a
major advance in understanding how bacteria divide. This could
lead to new antibiotic treatments that prevent dangerous
bacteria from multiplying.
Normally, bacteria divide by forming a ring that pinches the
cell in two. The ring is called a "Z ring" after the protein
FtsZ, which forms a ring-shaped scaffold and then squeezes it
smaller. In bacteria, the Z ring also contains a dozen other
proteins, all believed to be essential for division.
The Z ring normally pulls in on the cell membrane by binding
to another protein, FtsA, which has one end attached to the
inner cell membrane and the other end connected to FtsZ. When
the Z ring constricts, it completely pulls in the membrane and
nips the bacterium in two.
But cell biology research scientist Masaki Osawa, Ph.D., cut
FtsA out of the system by making an FtsZ that could bind
directly to the membrane, and called it "membrane targeted
FtsZ" or FtsZ-mts.
First, Osawa demonstrated that the new protein, FtsZ-mts,
assembled Z rings in bacteria.
Then he constructed a greatly simplified cell-division
machine in microscopic oil droplets, called liposomes, that
demonstrated the important role of FtsZ in the division
process. He was able to assemble Z rings in this completely
artificial system, the liposome, a tiny hollow sphere of fat
that mimics natural cell membranes.
To do this, Osawa mixed the liposomes with FtsZ and GTP, a
molecule that provides energy. On a microscope slide the
liposomes fused and stretched into tubes that mimicked the
shape of E. coli and other rod-shaped bacteria.
"It was a happy coincidence that the size and shape of the
liposomes was similar to that of rod-shaped bacteria," says
co-author Harold Erickson, professor of cell biology. "These
tubular liposomes are a new micro-structure, and their
formation is still a mystery."
During the experiment, fluorescently labeled FtsZ-mts was
initially on the outside of the liposomes, but some of the
tubular liposomes ended up with FtsZ on the inside. "We don't
know how this happens, but it is a key to the discovery," Osawa
Inside the liposome the FtsZ formed multiple closed rings
that aligned perpendicular to the length of the tube, just as Z
rings form in bacteria. They also slid back and forth, and
where they collided, they stayed together and formed brighter Z
rings. And as the Z rings grew in brightness, they visibly
pulled the wall of the liposome inward.
"The Z rings are clearly generating force and causing the
constriction," Osawa said. A movie the team made shows several
constrictions in the wall occurring at the sites of the bright
Z rings. When the GTP in the liposome is used up, the tube
eases out of its constrictions into its original shape.
"We believe our simple system may recreate the mechanism
that the earliest bacteria used to divide. They probably had
FtsZ alone," Erickson said. "Osawa's experiments show that
FtsZ, a membrane tether, and the inside surface of a tubular
membrane are all that's needed to assemble the Z ring and
generate a constriction force."
The artificial Z rings were not sufficient to pinch the
liposomes in half, "probably because their walls are much
thicker than the membrane of a bacterium," Osawa noted. "We are
now working to make thinner liposomes, so that we can achieve
Erickson said that FtsZ is the bacterial ancestor of
tubulin, the protein that makes the microtubules in animal
cells and is the target of a number of anti-cancer drugs like
taxol. Although FtsZ is not sensitive to taxol, anything
learned about the bacterial ancestor will help us understand
microtubules, which help animal cells to keep their shape and
control their movements, he explained.
NOTE: Movies of the constriction and release of the Z rings
in liposomes are available – please contact email@example.com