Good news! Like the discovery of the original penicillin, nature offers more antibiotics.
"... Named Clovibactin, the antibiotic appears to kill bacteria in an unusual way, making it more difficult for bacteria to develop any resistance against it. ...
Intriguingly, 99% of all bacteria are "unculturable" and could not be grown in laboratories previously, hence they could not be mined for novel antibiotics. Using the new device called iCHip, the U.S. researchers discovered Clovibactin in a bacterium isolated from a sandy soil from North Carolina, E. terrae ssp. Carolina. ..."
From the highlights and abstract:
"Highlights
• Clovibactin was discovered in a previously uncultivated bacterium
• Kills without resistance and is efficacious in a mouse model of S. aureus infection
• It blocks the cell wall biosynthesis by targeting distinct, essential precursors
• Clovibactin uses an unusual hydrophobic interface to target immutable pyrophosphate
Summary
Antimicrobial resistance is a leading mortality factor worldwide. Here, we report the discovery of clovibactin, an antibiotic isolated from uncultured soil bacteria. Clovibactin efficiently kills drug-resistant Gram-positive bacterial pathogens without detectable resistance. Using biochemical assays, solid-state nuclear magnetic resonance, and atomic force microscopy, we dissect its mode of action. 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. Selective and efficient target binding is achieved by the sequestration of precursors into supramolecular fibrils that only form on bacterial membranes that contain lipid-anchored pyrophosphate groups. This potent antibiotic holds the promise of enabling the design of improved therapeutics that kill bacterial pathogens without resistance development."
Graphical abstract
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