New catalyst redesigns macrolide antibiotics to kill MRSA
Get the Health newsletter
Daily health & science — research, biotech, public health, the studies worth knowing. Free.
- HAzc-(OMe)-OMe is a new azaadamantyl oxoammonium precatalyst whose compact structure lets it slip into sterically hindered regions on large macrolide molecules and selectively oxidize secondary alcohols into carbonyl groups.
- Olivia C. Langner and colleagues applied the catalyst to erythromycin A, clarithromycin, and azithromycin, oxidizing the C11 position on erythromycin A's main ring and the C4'' position on the sugar units of clarithromycin and azithromycin.
- The team synthesized 11 new antibiotic derivatives, of which six nitrogen-oxide analogs showed no bioactivity, while two keto-group (C=O) analogs at the C4'' position killed MRSA strains that resist the original drugs.
- The carbonyl modifications help antibiotics bypass the mph(C) resistance gene in Staphylococcus aureus, which normally adds a phosphate group that blocks the drug from binding to bacterial ribosomes.
- A couple of additional analogs demonstrated broad-spectrum activity against other pathogens, suggesting the catalyst could be deployed against multiple resistant strains, not just MRSA.
- The findings were published in ACS Central Science (DOI: 10.1021/acscentsci.5c02343), establishing a general method for atomic-level redesign of existing macrolide scaffolds.
Why it matters: Common macrolides like erythromycin A are losing ground to resistant strains such as MRSA, and developing entirely new antibiotics is slow and expensive. This catalyst offers a faster path: chemically reworking the drugs already in use. Two of 11 redesigned analogs killed MRSA where the originals fail, hinting at a way to revive and extend the macrolide class without starting from scratch.
