|Researchers Discover New Disease-Causing Bacterium in Patients
with Rare Immune Disorder
Scientists at the National Institute of Allergy and Infectious Diseases (NIAID),
part of the National Institutes of Health (NIH), have discovered a new bacterium
and determined that it can cause serious lymph node infections in patients with
chronic granulomatous disease (CGD) — a rare immune disorder that leaves
individuals susceptible to frequent and sometimes life-threatening fungal and
bacterial infections. Details of the discovery are described in the April 14
issue of PLoS Pathogens.
Researchers found the novel bacterium — which they named Granulobacter
bethesdensis in recognition of Bethesda, Md., the location of NIH headquarters — in
the inflamed lymph nodes of a patient with CGD. The bacterium is part of the
Acetobacteraceae family that includes several types of bacteria prevalent in
the environment and used industrially to produce vinegar. This is the first
time, however, that any member of that bacterial family has been known to cause
invasive human disease. Moreover, it represents yet another infection concern
for people with CGD, and possibly other individuals as well.
“The discovery of new bacteria is not uncommon, but discovering an organism
that causes human illness is certainly unique and warrants further research,” says
NIH Director Elias A. Zerhouni, M.D.
“This finding is an important discovery both in understanding new human pathogens
and in revealing a new source of illness in a patient population particularly
vulnerable to bacterial infections,” notes NIAID Director Anthony S. Fauci, M.D.
CGD, which affects one in 250,000 people worldwide, is one of 80 inherited immune
disorders known collectively as primary immune deficiencies. The disease is caused
by a genetic defect in an enzyme called phagocyte NADPH oxidase. Certain white
blood cells called neutrophils use this enzyme to generate hydrogen peroxide
that the cells need to kill bacteria and fungi. Because people with CGD cannot
effectively fight off bacterial and fungal invaders, these individuals are at
greater risk of developing serious infections of the skin, lungs, lymph nodes
and bones. People with CGD also are prone to developing obstructions in the digestive
and urinary tracts caused by swollen areas of inflamed tissues known as granulomas.
In July 2003, a 39-year old man with CGD was referred to NIH after experiencing
three months of unexplainable fever, chills, fatigue, night sweats and a 10-pound
weight loss. Doctors first gave him two different antibiotics, which did not
alleviate his symptoms. Two months later, he developed a painful swelling of
the lymph nodes at the base of his neck. Because the infection did not respond
to the antimicrobial medications and because there was no clear diagnosis for
his symptoms, the doctors removed several lymph nodes for examination. The lymph
nodes revealed extensive infection. Tests performed on three of the lymph nodes
confirmed a bacterial presence.
Using genetic sequencing, the researchers eventually determined that the bacteria
most closely resembled a member of the Acetobacteraceae family. Other tests revealed
that the patient’s immune system responded to the organism, indicating that it
had been exposed to and hence recognized the bacterium, and confirmed that the
newly discovered bacterium was indeed a pathogen.
To determine whether the bacterium specifically caused infection in connection
with CGD, the researchers inoculated healthy mice and mice genetically altered
to carry CGD with various amounts of the newly identified bacterium. Lymph nodes
recovered from the CGD mice revealed a similar condition to those of the CGD
patient. The lymph nodes of the disease-free mice appeared normal. Spleens recovered
from both types of mice showed evidence of the new bacterium but in much greater
amounts in the CGD mice. Genetic sequencing confirmed that the bacterium found
in the mice was identical to the organism isolated from the patient. The bacterium
was not fatal in the CGD patient nor the infected mice.
Since the initial acceptance of this study for publication, NIAID researchers
have isolated Granulobacter bethesdensis bacteria from two additional
patients with CGD who were experiencing clinical symptoms similar to those of
the initial CGD patient.
“Until recently, about 50 percent of infections in people with CGD could not
be diagnosed. Some of these patients were treated empirically with surgery and
broad spectrum drugs. Other infections were never successfully treated,” says
Steven M. Holland, M.D., chief of NIAID’s Laboratory of Clinical Infectious Diseases. “This
newly identified organism could help us identify the source of those infections
and allow for the development of targeted and curative therapies.”
According to the study’s lead author David E. Greenberg, M.D., a clinical fellow
in NIAID’s Laboratory of Clinical Infectious Diseases, further studies will be
- Compare the immune response to the new bacterium in healthy people and in
those with CGD
- Determine how the bacterium causes infection in people with CGD
- Explore the bacterium’s importance, if any, for the population at large
“The fact that the CGD mice survived the infection raises the question, What
is the critical component of the host’s immune defense, and which patients other
than those with CGD are most vulnerable to this newly discovered microbe?” Dr.
Holland adds. “I suspect the bacterium has been around as long as we have and
that we’ll find it has been busier than we knew in terms of disease activity
over the years.”
Researchers from the NIH Clinical Center and the National Cancer Institute,
additional components of NIH, also contributed to the research.
News releases, fact sheets and other NIAID-related materials are available on
the NIAID Web site at http://www.niaid.nih.gov.
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 transplantation and immune-related illnesses,
including autoimmune disorders, asthma and allergies.
The National Institutes of Health (NIH) — The Nation's 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 http://www.nih.gov.