Colorado State Scientists Tackle Genetic Makeup of Obscure Bacteria

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."