Chlamydia Escapes Defenses By Cloaking Itself with Lipids
DURHAM, N.C. -- Duke University Medical Center
microbiologists have discovered that the parasitic bacteria
Chlamydia escapes cellular detection and destruction by
cloaking itself in droplets of fat within the cell. The
researchers said that their findings represent the first
example of a bacterial pathogen "mimicking" such a structure,
or organelle, within a cell.
Not only do the findings suggest a novel mechanism of
bacterial infection, but the new insights into Chlamydia's
actions within infected cells provide rational targets for
potential drugs to halt the spread of the bacteria, said the
researchers. Chlamydia has been implicated in sexually
transmitted infections, atherosclerosis and some forms of
Chlamydia is an obligate intracellular parasite that
prospers within a host cell by hijacking the cell's internal
machinery to survive and replicate. The bacterium lives within
the cell in a protective capsule known as an inclusion. To
date, it has not been clearly understood how Chlamydia has
evolved to evade the cell's internal intruder alert system.
"In our experiments, we found that Chlamydia recruits lipid
droplets from within the cell and stimulates the production of
new droplets, which cover the surface of the inclusion,"
explained Yadunanda Kumar, Ph.D., a post-doctoral fellow in
Duke's Department of Molecular Genetics and Microbiology. "This
action of surrounding itself with lipid droplets may represent
an example of organelle mimicry, where the chlamydial inclusion
is protected from the cell's defenses by being perceived by the
cell as just another lipid droplet."
Kumar presented the results of the Duke research Dec. 11,
2005, at the 45th annual meeting of the American Society for
Cell Biology in San Francisco. The research was supported by
National Institutes of Health, the Pew Foundation and the
When these cloaked inclusions were treated with agents known
to inhibit the production of lipid droplets, the researchers
were able to significantly reduce the ability of the bacterium
"It has long been thought that lipid droplets within cells
were just passive repositories of energy for the cells," said
Duke microbiologist Raphael Valdivia, Ph.D., senior member of
the research team. "But now we are learning that these
structures appear to play important roles in lipid synthesis
and transport of cholesterol throughout the cell, and cell
For their experiments, the researchers studied Chlamydia
trachomatis, which is spread in humans by sexual contact and
can lead to such disorders urinary tract infections, eye
infections and arthritis.
Because the bacterium is an obligate parasite, researchers
cannot directly manipulate its genes. So the Duke team removed
genetic material from the bacterium and inserted them into
yeast cells, which share many common structures and features
with human cells.
When the researchers screened the chlamydial proteins in
yeast cells, they found four specific proteins that appeared to
recruit and spur the production of lipid droplets.
"Our findings provide evidence for a novel mechanism of
organelle subversion where Chlamydia recruits lipid bodies and
co-opts their function for survival," Valdivia said. "Chlamydia
may exploit lipid droplets to acquire lipids, modulate
inflammation or just for protection."
If unchecked, the inclusion will continue to grow until it
fills the entire cell, causing it to explode, releasing
thousands of bacteria ready to infect adjacent cells.
The findings also open the possibility of interfering with
Chlamydia's ability to infect cells by disrupting the
biosynthesis neutral lipids and lipid droplets. Further
research will be needed to develop such treatments, since the
agent the researchers used to inhibit lipid synthesis in the
laboratory is not a drug that is used clinically in humans.
The researchers believe that the same process may be
involved in other species of Chlamydia since the genetic
make-up of these bacteria has changed little over the hundreds
of millions of years of its successful ability to infect