Antimicrobial resistance is a major problem for human health and researchers worldwide are looking for new solutions. Few new antibiotics have been introduced into the clinic over the last decades and they often resemble older, already known antibiotics. Clovibactin was discovered by NovoBiotic Pharmaceuticals and microbiologist Kim Lewis, PhD, professor at Northeastern University. Earlier, they developed a device that allows the growth of unculturable bacteria. The majority (99%) of all bacteria are unculturable and could not be grown in laboratories previously, nor mined for novel antibiotics. Using the device, called iCHip, the U.S. researchers discovered Clovibactin in a bacterium isolated from a sandy soil from North Carolina: E. terrae ssp. Carolina. The researchers showed that Clovibactin successfully attacks a broad spectrum of bacterial pathogens and successfully treated mice infected with Staphylococcus aureus. Clovibactin blocks cell wall synthesis by targeting pyrophosphate of multiple essential peptidoglycan precursors (C55PP, lipid II, and lipid IIIWTA). Clovibactin uses an unusual hydrophobic interface to tightly wrap around pyrophosphate but bypasses the variable structural elements of precursors, accounting for the lack of resistance. The multi-target attack mechanism of Clovibactin blocks bacterial cell wall synthesis simultaneously at different positions. This improves the drug’s activity and substantially increases its robustness to resistance development. Here you can see a crystal structure of clovibactin (PDB code: 8CUG)

#molecularart ... #immolecular ... #antibiotic ... #clovibactin ... #resistance ... #peptide ... #xray

Structure rendered with @proteinimaging and depicted with @corelphotopaint