A new broad-range antibiotic kills a wide range of bacteria, including intractable Methicillin-Resistant Staphylococcus aureus (MRSA) infections which fail to respond to traditional antibiotics, and the Anthrax bacteria.
Scientists at Rockefeller University and Astex Pharmaceuticals jointly developed the new antibiotic, Epimerox, which uses weak spots in the bacterial cell walls as a point of attack. These weak spots are already a target for bacteriophage viruses, AKA ‘phage’ viruses, which infect and replicate inside bacteria.
Viral Tactics for Infecting Cells
Bacteriophage infect bacteria by targeting weaknesses in their cell walls, and this new antibiotic uses the same successful tactic. “We’re taking advantage of what phage have ‘learned’ during this period for us to identify new antibiotic targets we believe will escape the problem of resistance found for other antibiotics,” says senior author Vincent Fischetti, head of the Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York.
Fischetti and his colleagues used a molecule encoded with phage genes to identify a bacterial target enzyme called 2-epimerase, which is not native to the human body – an amino acid in the cell wall that dissolves in water.
In 2008, Fischetti’s lab, along with Rockefeller University’s Erec Stebbins and his colleagues in the Laboratory of Structural Microbiology, mapped the internal crystal structure of the 2-epimerase enzyme. The researchers identified a previously-unknown regulatory mechanism in 2-epimerase, and targeted it when developing a new multi-use antibiotic.
New Antibiotic Using Inhibitory Compounds
Raymond Schuch, a former postdoctoral researcher in Fischetti’s lab, tested the new antibiotic in mice infected with Bacillus anthracis; Epimerox fully protected the mice from anthrax bacteria. Further, the bacteria did not develop resistance to the inhibitor over the course of the research. The researchers also found that Epimerox was able to kill Methicillin Resistant Staphylococcus aureus (or MRSA) with no evidence of resistance developing, even after extensive testing.
“Since nearly all Gram-positive bacteria contain 2-epimerase, we believe that Epimerox should be an effective broad-range antibiotic agent,” says Fischetti. “The long-term evolutionary interaction between phage and bacteria has allowed us to identify targets that bacteria cannot easily change or circumvent. That finding gives us confidence that the probability for developing resistance to Epimerox is rather low, thereby, enabling treatment of infections caused by multi-drug-resistant bacteria such as MRSA. It is a very encouraging result at a time when antibiotic resistance is a major health concern.”
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