A clear molecular blueprint of globomycin, a substance which could be important in the design of new antibiotics, has been produced for the first time by researchers from the department of biochemistry immunology in Trinity College.
The importance of globomycin in the production of alternatives to antibiotics has been known for over ten years but progress before now had been stunted by the lack of a detailed structural blueprint.
World Health Organisation (WHO) has said that new drugs are in urgent need and has warned against an era antimicrobial resistance if action is not taken swiftly to combat the problem. Antibiotic resistance occurs naturally over time, as bacteria begins to adapt and become unresponsive to the medication, but this has been aggravated by misuse of the product in healthcare and in agriculture.
This could make common injuries and infections which have been treatable for decades a threat again, having already made some diseases, such as pneumonia, tuberculosis, blood poisoning and gonorrhoea, almost impossible to cure in some instances. Globomycin, however, has the ability to inhibit the enzyme LspA and hence prevent the production of cell wall proteins. It a crucial component in bacterial physiology and antibiotic resistance.
Professor of membrane structural and functional biology Martin Caffrey, who led the research, outlined the importance of the discovery in a statement: “The molecular form of the complex makes it a suitable target with which to explore the thousands of inhibitors developed for other medically relevant aspartyl protease enzymes. These include drugs that treat high blood pressure and HIV AIDS.”
This critical factor of globomycin is that it functions as a narrow spectrum microbial, meaning that it can target the specific active site of certain species of bacteria, making the risk of a generalised antibiotic resistance response much less likely.
This important fact is something Caffrey highlighted. “Globomycin and its enzyme target are networked to such a degree that any mutation perturbing the drug’s interaction would also likely impact on how the bacteria functions. Antibiotics that do not elicit resistance are invaluable to medicine, and this work might inspire the design of such drugs.”
The blueprint was produced based on a technique called “X-Ray Crystallography” where Scientists produce crystals of the substance of interest and then fire finely focused and powerful X-ray beams at the crystals to discover the structure.
A report of the research was published in the latest issue of the journal Science on Thursday evening, titled “Structural basis of lipoprotein signal peptidase II action and inhibition by the antibiotic globomycin.” The work was supported by Science Foundation Ireland.