A new broad-spectrum antibiotic, developed jointly by scientists at the Rockefeller University and Astex Pharmaceuticals, has been found to kill a wide range of bacteria, including drug-resistant Staphylococcus bacteria that do not respond to traditional drugs. The antibiotic, Epimerox, targets weaknesses in bacteria that have long been exploited by viruses that attack them, known as phage, and has even been shown to protect animals from fatal infection by Bacillus anthracis, the bacteria that causes anthrax.
Target selection is critical for the development of new antimicrobial agents. To date, most approaches for target selection have focused on the importance of bacterial survival. However, in addition to survival, the Rockefeller scientists believe that molecular targets should be identified by determining which cellular pathways have a low probability for developing resistance.
For a billion years, phages repeatedly have infected populations of bacteria, and during this period of time they have identified weaknesses in the bacterial armor, says senior author Vincent A. Fischetti, professor and head of the Laboratory of Bacterial Pathogenesis and Immunology. Were taking advantage of what phage have learned during this period for us to identify new antibiotic targets that we believe will escape the problem of resistance found for other antibiotics.
The path to identification of this new target spanned more than seven years of effort. Fischetti and his colleagues used a phage-encoded molecule to identify a bacterial target enzyme called 2-epimerase, which is used by Bacillus anthracis to synthesize an essential cell wall structure. In 2008, Fischettis lab, with Rockefellers Erec Stebbins and his colleagues in the Laboratory of Structural Microbiology, solved the crystal structure of this enzyme. Based on this work, the researchers identified a previously unknown regulatory mechanism in 2-epimerase that involves direct interaction between one substrate molecule in the enzymes active site and another in the enzymes allosteric site. Fischetti and his colleagues chose to target the allosteric site of 2-epimerase to develop inhibitory compounds, because it is found in other bacterial 2-epimerases but not in the human equivalent of the enzyme.
Through the collaboration with Astex, an inhibitor of 2-epimerase named Epimerox was developed. Raymond Schuch, a former postdoctoral researcher in Fischettis lab, tested the inhibitor in mice infected with Bacillus anthracis. He found that not only did Epimerox protect the animals from anthrax, but the bacteria did not develop resistance to the inhibitor. The researchers also found that Epimerox was able to kill methicillin-resistant Staphylococcus aureus (MRSA) with no evidence of resistance even after extensive testing. Their work was published this week in PLoS One.
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.
Source: Rockefeller University
Â
A Helping Hand: Innovative Approaches to Expanding Hand Hygiene Programs in Acute Care Settings
July 9th 2025Who knew candy, UV lights, and a college kid in scrubs could double hand hygiene adherence? A Pennsylvania hospital’s creative shake-up of its infection prevention program shows that sometimes it takes more than soap to get hands clean—and keep them that way.
Broadening the Path: Diverse Educational Routes Into Infection Prevention Careers
July 4th 2025Once dominated by nurses, infection prevention now welcomes professionals from public health, lab science, and respiratory therapy—each bringing unique expertise that strengthens patient safety and IPC programs.
How Contaminated Is Your Stretcher? The Hidden Risks on Hospital Wheels
July 3rd 2025Despite routine disinfection, hospital surfaces, such as stretchers, remain reservoirs for harmful microbes, according to several recent studies. From high-touch areas to damaged mattresses and the effectiveness of antimicrobial coatings, researchers continue to uncover persistent risks in environmental hygiene, highlighting the critical need for innovative, continuous disinfection strategies in health care settings.