Research | Publications | Lab Members | Nucleic Acids Core Facility | S A Center for Medical Mycology
Brian L. Wickes, Ph.D.
Room 5.027V Tel: (210) 567-3938Fax: (210) 567-6612Email:
My laboratory is interested in the biology and molecular biology of medically important fungi. The fungus that we spend the most time studying is Cryptococcus neoformans, a basidiomycetous yeast that is closely related to mushrooms and a number of plant pathogens. C. neoformans is ubiquitous in the environment and is found globally. Infections typically occur via a pulmonary route after spores or yeast cells are inhaled. Once the lung is colonized, the fungus can remain there or disseminate to other parts of the body. A wide variety of mammals are susceptible to C. neoformans infections. In humans, the most frequent manifestation of infection is meningitis. Typically, immunosuppressed individuals are at the highest risk for infection although the fungus can infect healthy individuals. AIDS patients are at greatest risk for cryptococcosis, with 5-10% infected at the peak of the epidemic. In undeveloped countries, the number can be as high as 30%. If untreated, cryptococcosis is almost 100% fatal.
Our major interest in C. neoformans concerns the role that mating plays in virulence. The fungus is heterothallic with a bipolar mating system containing two mating types, MATα and MATalpha. In nature, MATalpha cells significantly out number MATα cells in population surveys. This bias is also reflected in clinical isolates where MATα cells are rarely isolated from patients. Studies in our laboratory have shown that MATalpha cells are more virulent than MATα cells. In addition, we and others, have found that a number of genes that are required for fertility are also required for virulence of the organism. More importantly, a number of genes that are involved in mating also control certain aspects of fungal morphology. Since it still remains unclear as to what morphology is responsible for infections researchers will continue to dissect the mating pathway and other pathways that regulate fertility and development.
A second fungus that we work with in our laboratory is Candida albicans. C. albicans is an ascomycete, which is closely related to the model yeast, Saccharomyces cerevisiae. This fungus is the most important and most frequently isolated human fungal pathogen. It is capable of infecting virtually every site in the body and although C. albicans is a normal commensal of humans and other mammals, infections can be life threatening. Our specific interests in C. albicans concern its ability to form biofilms. C. albicans can form biofilms on virtually any implantable device. Similar to bacterial biofilms, once a C. albicans biofilm is formed, it is virtually impossible to treat with antibiotics, consequently the device must be removed, sometimes at great expense or risk. We are interested in the mechanisms that underlie biofilm formation and are presently using microarrays to search for genes required for biofilm formation. We are also interested in the genetic basis for the increased drug resistance of cells that are growing in the biofilm phenotype. The use of microarrays to study C. albicans biofilms has allowed us to identify a number of genes that are only expressed when cells grow as a biofilm. The genes are currently being disrupted in order to study their effect on the ability of the strain to form a biofilm as well as any change in antifungal susceptibility.
A third fungus that we work with is Aspergillus fumigatus. A. fumigatus is a ubiquitous fungus that grows exclusively in a mold-like or filamentous morphology. The fungus is classified as an ascomycete and is related to Aspergillus nidulans and Neurospora crassa, two model filamentous fungi. Although A. fumigatus is one of the most common fungi that humans encounter, it poses little problems for healthy people. However, for certain types of immunosuppressed patients, infections can be fatal. In fact, we perform a number of epidemiological studies on A. fumigatus because it is a frequent cause of outbreaks in hospitals. The fungus is particularly dangerous for patients undergoing bone marrow transplantations since infections have a very low cure rate and can be uniformly fatal. We perform studies to determine the relatedness of populations of strains recovered from outbreaks using a variety of fingerprinting techniques.
Lab Rooms: 5.027V
Nucleic Acids Core Facility Personnel (Room 4.059V)