Researchers Put Potent Staph Killer To The Test, Hope For New Drug Treatment
Posted Apr 04 2011 9:14pm
Standard antibiotics, and even those reserved for the most defiant infections, are fighting an uphill battle against the evolutionary ingenuity of bacterial defenses. Staphylococci, and especially methicillin-resistant Staphylococcus aureus (MRSA), is a particular scourge in hospitals, and is increasingly infecting people outside of health care settings. But a promising new MRSA killer — a genetically engineered enzyme first created at Rockefeller — is now being tested in human skin cells and will soon advance to trials in a new animal model, the minipig. The enzyme has been recently been shown to target and kill MRSA in mice with greater efficiency than the only approved topical treatment for such infections, a drug called mupirocin. Researchers say the work is steadily advancing through stages that could lead to the development of a frontline drug to fight MRSA, which costs hospitals billions of dollars a year.
“It’s the start of a new class of drugs,” says Mina Pastagia, a clinical scholar in Vincent Fischetti’s Laboratory of Bacterial Pathogenesis and Immunology, who is leading the current research. “We’re starting from scratch, and it looks promising.”
The work stems from the genetic engineering of a lysin, a protein derived from viruses that have been infecting bacteria for billions of years, by a team of researchers in Fischetti’s lab. Nature produces countless lysins that can fight staph, but when they are recombinantly produced in the laboratory they are often insoluble or have low activity. Lysins have two basic parts. One, the binding region, recognizes the target bacteria and latches hold. The second bores holes through the bacterium’s cell wall, killing the organism. The Fischetti teams tried combinations of these two parts from about two dozen naturally occurring lysins and came up with a chimera that is easy to produce, soluble, and very active. This new creation — named chimeric lysin for staphylococci or ClyS — retained the power to kill MRSA, and was especially effective in a mouse model when used in combination with oxacillin, an antibiotic that is powerless against MRSA on its own. “The fact that lysins work synergistically with antibiotics to increase their effectiveness, particularly those to which bacteria are resistant, will enable ‘shelved’ antibiotics to be reinstated, increasing our antibiotic armamentarium to these pathogens” says Fischetti.
Standard antibiotics, and even those reserved for the most defiant infections, are fighting an uphill battle against the evolutionary ingenuity of bacterial defenses. Staphylococci, and especially methicillin-resistant Staphylococcus aureus (MRSA), is a particular scourge in hospitals, and is increasingly infecting people outside of health care settings. But a promising new MRSA killer — a genetically engineered enzyme first created at Rockefeller — is now being tested in human skin cells and will soon advance to trials in a new animal model, the minipig. The enzyme has been recently been shown to target and kill MRSA in mice with greater efficiency than the only approved topical treatment for such infections, a drug called mupirocin. Researchers say the work is steadily advancing through stages that could lead to the development of a frontline drug to fight MRSA, which costs hospitals billions of dollars a year.
“It’s the start of a new class of drugs,” says Mina Pastagia, a clinical scholar in Vincent Fischetti’s Laboratory of Bacterial Pathogenesis and Immunology, who is leading the current research. “We’re starting from scratch, and it looks promising.”
The work stems from the genetic engineering of a lysin, a protein derived from viruses that have been infecting bacteria for billions of years, by a team of researchers in Fischetti’s lab. Nature produces countless lysins that can fight staph, but when they are recombinantly produced in the laboratory they are often insoluble or have low activity. Lysins have two basic parts. One, the binding region, recognizes the target bacteria and latches hold. The second bores holes through the bacterium’s cell wall, killing the organism. The Fischetti teams tried combinations of these two parts from about two dozen naturally occurring lysins and came up with a chimera that is easy to produce, soluble, and very active. This new creation — named chimeric lysin for staphylococci or ClyS — retained the power to kill MRSA, and was especially effective in a mouse model when used in combination with oxacillin, an antibiotic that is powerless against MRSA on its own. “The fact that lysins work synergistically with antibiotics to increase their effectiveness, particularly those to which bacteria are resistant, will enable ‘shelved’ antibiotics to be reinstated, increasing our antibiotic armamentarium to these pathogens” says Fischetti.