Newly Engineered Enzyme Is A Powerful Staph Antibiotic
Posted Feb 05 2010 2:41pm
With their best chemical antibiotics slowly failingscientists are increasingly looking to nature for a way to control deadly staph bacteria — the culprit behind most hospital infections. Naturally toxic for bacteriaenzymes called lysins have the promising ability to obliterate staphbut the problem is producing large enough quantities of them to study how they work. Rockefeller University scientists have now overcome this barrier by engineering a lysin that not only kills multidrug-resistant Staphylococcus aureus (MRSA) in micebut also works synergistically with traditional antibiotics that have long been shelved due to resistance.
For the past five yearsVincent A. Fischettihead of the Laboratory of Bacterial Pathogenesis and Immunologyand his colleagues have tried to clone a lysin that specifically targets staphbut they always ran into the same problem. Although hundreds of thousands of lysins could be expressed in an engineered cellthey all would stick together forming an insoluble clumprendering them inactive. “They were useless; a real thorn in our side,” says Fischetti. “We’ve come across some problems cloning lysins for other bacteriasuch as strepbut nothing to this extent.”
Lysinsproteins derived from the viruses that have been infecting bacteria for billions of yearshave two basic components. One acts as a recognition system to identify the specific bacteria species it has evolved to target; the other works like a molecular power drill that bores holes through the bacterium’s cell wallkilling the organism. Togetherthese two components work so quickly and so efficiently that bacteria have no time to develop resistance.
With their best chemical antibiotics slowly failingscientists are increasingly looking to nature for a way to control deadly staph bacteria — the culprit behind most hospital infections. Naturally toxic for bacteriaenzymes called lysins have the promising ability to obliterate staphbut the problem is producing large enough quantities of them to study how they work. Rockefeller University scientists have now overcome this barrier by engineering a lysin that not only kills multidrug-resistant Staphylococcus aureus (MRSA) in micebut also works synergistically with traditional antibiotics that have long been shelved due to resistance.
For the past five yearsVincent A. Fischettihead of the Laboratory of Bacterial Pathogenesis and Immunologyand his colleagues have tried to clone a lysin that specifically targets staphbut they always ran into the same problem. Although hundreds of thousands of lysins could be expressed in an engineered cellthey all would stick together forming an insoluble clumprendering them inactive. “They were useless; a real thorn in our side,” says Fischetti. “We’ve come across some problems cloning lysins for other bacteriasuch as strepbut nothing to this extent.”
Lysinsproteins derived from the viruses that have been infecting bacteria for billions of yearshave two basic components. One acts as a recognition system to identify the specific bacteria species it has evolved to target; the other works like a molecular power drill that bores holes through the bacterium’s cell wallkilling the organism. Togetherthese two components work so quickly and so efficiently that bacteria have no time to develop resistance.