Reseacher at Montana State working on vaccine for fungal infections

Jim Cutler

White blood cells called phagocytes play an essential role in one of the most extraordinary and cunning methods developed for killing invading fungal cells.

According to expert Dr. Jim E. Cutler, a professor of microbiology at Montana State University, rather than entering their target cells like viruses, fungal pathogens such as Candida albicans, a yeast cell, spread by attaching themselves to the surface of host cells.

In defense, when C. albicans invades, specific antibodies in our system coat the fungal cell and activate what is called the complement cascade, a system of enzymes and proteins that cover the surface of the fungal cell. The complement cascade promotes a rapid association of the fungal cells with phagocytes. 3It's a favorable situation for the host,2 Cutler says.

In other words, the complement factors that cover the surface of the yeast fungal cell draw it and the phagocyte together. The enzymes and proteins that cover C. albicans act as a collective beacon that 3complements2 a cellular receptor on the phagocyte, which uses the beacon to hone in on the fungal cell for the kill.

Cutler, the 13th annual Science in Medicine WWAMI lecturer, will give a talk on his research, titled 3Resolving a Controversy: The Role of Antibodies in Defense Against Candidiasis,2 on Friday, May 22, from noon to 1 p.m. in room T-625 of the Health Sciences Center.

C. albicans is present on the skin and in the mouth, intestinal tract, and vagina. When it multiplies, it usually causes minor skin or mucous membrane infections. It is among the leading causes of nosocomial infectious diseases, which occur due to a patient's stay in the hospital. Potentially fatal infections can occur in immunocompromised patients as a result of dissemination of the fungus to internal organs.

Cutler has found that antibodies play a role in defending against C. albicans and has developed an effective vaccine that works in mice.

Among Cutler's first steps was to describe the chemical and structural basis of the 3adhesion event,2 the moment the fungal cell sticks to a host surface. The branch-like molecular structures the fungal cells use to attach themselves are 3adhesins.2

3The bottom line is that there are antibodies against certain parts of the adhesin complex, while antibodies to other parts of the complex do not protect the host,2 he said.

This is controversial, however. 3If we say that antibodies are protecting the host, then why are people still dying from the disease even though antibodies can be detected in their serum,2 Cutler said.

The answer is that you have to have the right ones. Production of these antibodies takes a minimum of 7 to 10 days. For a protective antibody to help the host, it must be present prior to the invasion by C. albicans. Cutler and his colleagues speculate that in some people these kinds of antibodies are present as a result of prior exposure to the fungus.

The adhesin complex involved in the attachment of the fungal cell to the host is very large. Antibodies can attach specifically to very small parts of the complex. The host defeats the fungus by developing antibodies against 3the correct2 parts of the adhesin complex, Cutler said.

All people are likely to have the fungus as a member of the normal flora from time to time. In women, these fungi sometimes invade the vaginal epithelium and cause yeast infections, but usually they do no harm in the vaginal tract.

When we become immunodeficient, however, the fungus can cause skin disease or become deep-seeded in organs. It can even go to the brain. 3If things go awry and C. albicans gets out of hand, you can begin to develop a disease state,2 Cutler said.

People who are going to be at high risk of developing serious conditions due to C. albicans could in the future receive a vaccine that induces production of protective antibodies, Cutler said. Risk factors would include those people who are going to have abdominal surgery; transplantations, including bone marrow, kidney or heart transplants; and anyone who knows in advance that they are likely to have a long hospital stay. Cutler hopes to conduct clinical trials of the candidate vaccine he and his colleagues have developed.

Cutler has been working on fungal pathogens since the 1970s. He received a B.S. in 1967 and an M.S. in 1969 from California State University-Long Beach and a Ph.D. in microbiology from Tulane University Medical School in 1972.

Cutler was a postdoctoral fellow at the National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories. He has been a professor of microbiology at MSU since 1989.

Will Morton