http://www.physorg.com/printnews.php?newsid=77811326
9/18/2006 11:45 PM
Researchers Uncover a Secret of the Black Death
Yersinia pestis, the bacteria that causes plague, is a sneaky little
intruder with a remarkable ability to evade the bodys immune
system. Upon entering an organism, Y. pestis employs a variety
of strategies to slip below the radar of the innate immune
responsethe bodys front line of defense against invading
pathogensand in many cases kills the host before its more
specific antibacterial response can develop.
It is this stealth and virulence that has made plague one of
the most
feared diseases in human history, blamed for more than 200 million
deaths. While human cases of plague in the United States are now
rare, a few thousands worldwide are infected each year and with the
potential of intentional misuse of Y. pestis, the efforts to develop
better treatments and a vaccine are now no less important than they
were when the bacterium was first identified.
Researchers at the University of Massachusetts Medical School have
made a significant breakthrough in the field, modifying Y. pestis
with a gene found in another commonly known bacterium,
effectively rendering it unable to cause plague. In Virulence factors
of Yersinia pestis are overcome by a strong LPS response, to be
published in the October issue of Nature Immunology, Egil Lien,
PhD, assistant professor of medicine and molecular genetics &
microbiology, Jon D. Goguen, PhD, associate professor of molecular
genetics and microbiology, graduate student Sara Montminy and
colleagues, also describe the effectiveness of the modified bacteria
as a vaccine.
Innate immunitythe precursor to the adaptive immune system in
mammalsacts as the first line of defense against a range of
pathogens. Prior to the adaptive immune response that involves the
bodys production of antibodies that precisely target and combat the
invader, the innate immune system reacts
immediately upon
infection. Recent research has described an important class of sensor
molecules, collectively known as Toll-like receptors (TLRs) that
recognize pathogens right away, activating the critical signaling
pathways that stimulate this initial immune response. Activation of
the TLRs also improves the adaptive immune response; in fact,
Print the story http://www.physorg.com/printnews.php?newsid=77811326
2 of 3 9/18/2006 11:45 PM
many vaccines include ingredients known as adjuvants that stimulate
the innate immune response.
Intriguingly, the bacteria Y. pestis has an unusual
temperature-dependent ability to evade this system.
Lipopolysaccharide, or LPS, is a major component of the membrane
of this type of bacteria, contributing to structural integrity but also
typically provoking a strong response from the immune system.
When at human body temperature (37ºC), Y. pestis produces an LPS
with a poor ability to activate TLR4, one of the major mammalian
innate immunity toll-like receptors; at lower temperatures, for
example that of a flea that transmits the disease (26º), the LPS
produced was distinctly more potent and thus triggered TLR4.
Recognizing that this difference was not found in E. coli, a common
bacterium with some similarities to Y. pestis, Lien identified an E.
coli gene that was important for the production of LPS but that was
missing in Y. pestis. Using this gene to generate new strains of Y.
pestis, researchers produced Y. pestis strains that were recognized
much more easily by innate immunity and TLR4 at both
temperatures. Importantly, the investigators found that the new
strains were unable to cause plague and mortality in normal mice;
the strains were at least a million times less virulent than the wild
type bacteria.
Our findings describe one of the secrets of the Black Death, Lien
said. These results suggest that the production of surface lipids
with poor ability to activate innate immunity is essential for Y. pestis
to be so deadly, and, in fact, for the ability of the bacteria to cause
plague. We expect this strategy to also
be important for various
other human bacterial pathogens.
This result is quite surprising, in part because plague research has
focused on many active things that the bacteria do to protect
themselves from host defenses, including injecting toxins directly
into cells of the immune system that try to engulf them," notes
Goguen. Apparently all of this is useless unless the bugs can also
hide from TLR4. Stealth is important.
Significantly, Lien and colleagues also determined that these new
harmless strains of Y. pestis could serve as vaccines. After
vaccinating mice with the modified strain of Y. pestis, the
Print the story http://www.physorg.com/printnews.php?newsid=77811326
3 of 3 9/18/2006 11:45 PM
investigators re-introduced the virulent strain after 30 days and
found that all of the animals were protected from developing plague.
These findings show that the production of avirulent bacterial strains
with enhanced ability to stimulate the immune system could
constitute a new general method for generating effective vaccines.
Source: University of Massachusetts Medical School
This news is brought to you by PhysOrg.com
Talk is cheap. Use Yahoo! Messenger to make PC-to-Phone calls. Great rates starting at 1¢/min.
_______________________________________________ Biofuel mailing list Biofuel@sustainablelists.org http://sustainablelists.org/mailman/listinfo/biofuel_sustainablelists.org
Biofuel at Journey to Forever: http://journeytoforever.org/biofuel.html Search the combined Biofuel and Biofuels-biz list archives (50,000 messages): http://www.mail-archive.com/biofuel@sustainablelists.org/
