|Newly Found Sensing System Enables Certain Bacteria
to Resist Human Immune Defenses
Researchers at the National Institute of Allergy and Infectious
Diseases (NIAID), a component of the National Institutes of Health,
have discovered a survival mechanism in a common type of bacteria
that can cause illness. The mechanism lets the bacteria protect
itself by warding off attacks from antimicrobial peptides (AMPs),
which are defense molecules sent by the body to kill bacteria.
Bacteria are divided into two types, gram-positive and gram-negative,
with the primary difference being the nature of the bacterial cell
wall. Little is known about how gram-positive bacteria — such
as those that can lead to food poisoning, skin disorders and toxic
shock — avoid being killed by AMPs. AMPs are made by virtually all
groups of organisms, including amphibians, insects, several invertebrates
and mammals, including humans.
“Gram-positive bacteria are major
threats to human health, especially due to increasing problems
with drug resistance, and these findings may help chart a path
to designing new drugs to bolster our antimicrobial treatment options,” notes
NIAID Director Anthony S. Fauci, M.D.
Led by Michael Otto, Ph.D., of NIAID’s Rocky Mountain Laboratories
(RML), the scientists used the gram-positive bacterium Staphylococcus
epidermidis to study its response to a specific human AMP,
human beta defensin 3. S. epidermidis is one of several hard-to-treat
infectious agents that can be transmitted to patients in hospitals
via contaminated medical implants. Findings by Dr. Otto’s research
group are published in the May 29 issue of the Proceedings
of the National Academy of Science. Other well-known types
of gram-positive bacteria include agents that cause anthrax, strep
throat, flesh-eating disease and various types of food poisoning.
In gram-negative bacteria — such as those that cause plague
and salmonellosis — a sensory and gene regulation system
named PhoP/PhoQ protects invading bacteria, and scientists believe
if they develop a better understanding of this system they could
develop new drugs that are more effective at protecting people
Likewise, now Dr. Otto and his research group are hoping for similar
possibilities for gram-positive bacteria with their discovery of “aps,” which
stands for antimicrobial peptide sensor. Aps has three parts: apsS,
the sensor region; apsR, the gene regulation region; and apsX,
which has an unknown function that Dr. Otto’s group is investigating.
Studies show that all three components of aps must be present for
the system to function and effectively protect bacteria from AMPs.
“We are aware that for gram-negative bacteria, PhoP/PhoQ has been
called a premier target for antimicrobial drug discovery, but little
corresponding work has been done with gram-positive bacteria,” Dr.
Otto says. “Our group is excited by what we have demonstrated — an
efficient and unique way that gram-positive bacteria control resistance — and
we are continuing our investigation of the aps sensing system being
used for drug development.”
NIAID is a component of the National Institutes of Health. NIAID
supports basic and applied research to prevent, diagnose and treat
infectious diseases such as HIV/AIDS and other sexually transmitted
infections, influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research on basic immunology,
transplantation and immune-related disorders, including autoimmune
diseases, asthma and allergies. News releases, fact sheets and
other NIAID-related materials are available on the NIAID Web site
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Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.