Colorado State Scientists Tackle Genetic Makeup Of Obscure Bacteria
Thursday, November 20, 1997
FORT COLLINS--A pair of Colorado State University
researchers have launched two separate five-year studies into
what causes a bacteria found virtually everywhere to mysteriously
single out AIDS patients as hosts for disease.
Andrea Cooper and Julie Inamine, both scientists in the
university's noted Mycobacteria Research Laboratory, each
received grants worth nearly $1 million to investigate what
triggers the bacteria to proliferate and cause disease in AIDS
patients even though humans are not natural hosts for the
bacteria.
The separate studies, funded by the National Institutes of
Health, also will investigate why some strains of the bacteria,
called Mycobacterium avium, seem harmless and receptive to drugs,
while other strains reproduce in the body unchecked and are drug-
resistant.
The Colorado State researchers say the presence of
Mycobacterium avium in AIDS patients is particularly troubling
because it causes a disease that is resistant to standard drug
treatments, thus requiring large doses of drug combinations.
Mycobacterium Avium Complex Disease, also called MAC, occurs
in as much as 40 percent of people with AIDS and often is
diagnosed toward the latter part of the patient's life. It can
trigger a host of serious problems, including blood infections,
hepatitis, skin lesions and pneumonia. Because Mycobacterium
avium can be found virtually everywhere, AIDS patients can be
exposed by taking a shower or eating food that contains the
bacteria.
"Why, of all the bacterial pathogens out there, do AIDS
patients seem to be affected by this one in particular?" Cooper
said. "In many respects, this is a mystery. We are trying to find
out what physiological responses are triggering the bacteria to
develop into a disease in this particular group of people."
Although Mycobacterium avium belongs to the same family of
well-studied bacteria that cause tuberculosis and leprosy, not
much is known about how it interacts with cells or why it can
grow to such large numbers in the body without causing disease.
"Unlike the bacteria that causes tuberculosis and leprosy,
Mycobacterium avium accumulates in the body much more slowly and
doesn't explode into a full-blown disease until the T-cell count
is very low," Cooper said. "Our research focuses on the theory
that at some point, there may be a cause and effect between low
T-cells, presence of the bacteria and the emergence of the
disease."
Meanwhile, Inamine's research will look at the molecular and
genetic differences between the two main types of Mycobacterium
avium. The goal is to identify the genes responsible for allowing
one strain of the bacteria to circumvent the body's defense
mechanisms and cause disease and the other strain to not cause
disease and be receptive to drugs. By pinpointing what chemical
reactions or molecular processes within the bacteria allow it to
thrive, researchers can develop drugs that turn off those
reactions and prevent the disease altogether.
"We have some tantalizing ideas on what might be causing the
bacteria to be pathogenic, or capable of causing disease,"
Inamine said. "There are pieces of the chromosome missing from
each of the strains, but in different regions. We think this
could provide some key clues as to where to look to find the
genes that produce the bacteria that cause disease and the
bacteria that don't."
Once these genes have been identified, there is a
possibility that techniques could be used to transfer genes that
make the bacteria susceptible to drugs into the strain of
bacteria that is not currently receptive to drugs and triggers
disease.
"One of the important aspects of this research is that not
much is known about what makes this organism resistant to drugs
and what causes disease in some people but not others," Inamine
said. "The long-term goal of this project is to tackle this
bacteria at a molecular level; to define what causes drug
resistance and virulence in these specific strains so we can
manipulate those effects and prevent disease."
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