JAR1, a Dominant Gene Conferring Resistance to Amphotericin B in Saccharomyces cerevisiae

Infectious diseases are the cause of death for over 1 million people a year in the United States alone. Drug resistance in infectious microbes is an increasing problem. This study focuses on antibiotic resistance in fungal infections, using Saccharomyces cerevisiae as the model of study. Spontaneous mutations in this yeast resulted in a yeast strain with the ability to grow in the presence of the antifungal drug amphotericin B. This yeast isolate, named JAR1, was genetically analyzed to determine how many mutated genes were responsible for the resistant phenotype, and whether the allele was dominant or recessive. The results indicate that the ability of JAR1 to grow in the presence of amphotericin B is due to a single dominant mutation. I. BACKGROUND drug and inactivate it. This type of resistance commonly arises in penicillinresistant strains. A second way that resistance can occur is through the exclusion of the drug from the cell. In this case, the bacterial cell is altered in a way that prevents the antibiotic from penetrating the cell membrane. Thirdly, the binding site for the antibiotic can be altered in the bacterial cell. Many antibiotics act as competitive inhibitors; altering the active site of the inhibited enzyme in a way that allows normal substrates to continue binding but prevents the antibiotic inhibitor from binding is an effective way to resist the drug action. The last known way of resistance in bacteria occurs when some bacteria use membrane pumps to remove the drug from the cell before the antibiotic has a chance to interact with its molecular targets [1]. All of these types of resistance are caused by mutations that alter bacterial physiology so that the drug can no longer exert its effect. Bacterial infections are often treated with antibiotic drugs. However, the misuse of antibiotic drugs has caused drug resistant bacteria to become an increasing problem. Antibiotic misuse includes unnecessary antibiotic prescriptions and patients not completing the full course of their prescription, both of which enable the most drug resistant bacteria to survive, replicate, and spread to other hosts. The study of drug resistance in bacteria has found four major ways that resistance occurs at the molecular level. First, the drug could be destroyed or inactivated. This occurs when the bacteria express enzymes that chemically alter the First, the drug could be destroyed or inactivated. This occurs when the bacteria express enzymes that chemically alter the † Correspondence may be addressed electronically to any of the authors: Drug resistance has been studied extensively in bacteria, and is expected to behave similarly in fungi. Like bacterial infections, fungal infections have a great impact on our society. Infectious fungi are a major cause of death in AIDS patients. These infectious fungi act as opportunistic Joyce.Iwema@trnty.edu, Katherine.force@trnty.edu, Rrylaarsdam@trnty.edu Correspondence may also be mailed to: Robin Pals-Rylaarsdam, Ph.D. Trinity Christian College Biology Department 6601 West College Drive Palos Heights, IL 60463