Biochemical and regulatory mechanisms involved in secondary metabolism and antibiotic resistance in actinobacteria

点击翻译按钮获取中文摘要

Infections caused by antibiotic resistant bacteria are a major problem, but the recent emergence and spread of bacterial diseases previously thought to be under control is cause for even greater concern. Clavulanic acid is a drug used in the treatment of infections caused by certain bacteria that are resistant to the penicillin family of antibiotics. When clavulanic acid is given in combination with a penicillin-type antibiotic, it restores the ability of the antibiotic to act against the targeted organism by silencing its resistance mechanism. Clavulanic acid is produced by Streptomyces clavuligerus, a bacterium that is related to a group of microorganisms (the Actinobacteria) that produce many medicinally important compounds. There is great interest in studying antibiotic production by the Actinobacteria with the aim of finding ways to improve antibiotic yields and to identify new molecules for novel applications. Industrial production of clavulanic acid for use in drug formulations is valued in excess of one billion dollars annually and my work will be crucial in determining how production takes place and how it is controlled in S. clavuligerus. I am interested in identifying key steps and regulatory mechanisms involved in the biosynthesis of clavulanic acid with the aim of improving its production. The long term goal of my research is to fully understand the biosynthesis and regulation of clavulanic acid so that the information gained can be applied more broadly to S. clavuligerus to produce new molecules for potential medicinal applications. My research program will contribute significantly to the training of students and other highly qualified personnel, which will benefit Canada by providing access to individuals skilled in the discovery of new natural products for targeting antibiotic resistant bacterial infections, in addition to other medicinal applications.