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Targeted screening for elongation factor Tu binding antibiotics
E Selva1, N Montanini, S Stella
1Lepetit Research Center, Gerenzano (VA), Italy.
The Journal of Antibiotics
|January 1, 1997
Summary
Researchers developed a novel screening method to find new antibiotics targeting elongation factor Tu (EF-Tu). This approach led to the discovery of novel EF-Tu-binding thiopeptide antibiotics, expanding the arsenal against bacterial infections.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Discovery
Background:
- Antibiotic resistance necessitates the discovery of novel antimicrobial agents.
- Elongation Factor Tu (EF-Tu) is a validated target for antibacterial compounds.
Purpose of the Study:
- To develop and implement a screening method for identifying antibiotics that inhibit EF-Tu.
- To discover novel EF-Tu-targeting antibiotics from microbial sources.
Main Methods:
- A screen was designed based on the principle of selecting antimicrobial activities antagonized by exogenous EF-Tu.
- High-throughput screening of 47,000 microorganisms was performed.
- Characterization of newly discovered antibiotic compounds.
Main Results:
- The screen successfully identified known EF-Tu inhibitors, such as kirromycin.
- Several microbial producers of kirromycin-type antibiotics were detected.
- Two novel thiopeptide antibiotics, GE2270 and GE37468, acting on EF-Tu, were discovered.
Conclusions:
- The developed screening method is effective for discovering EF-Tu-targeting antibiotics.
- GE2270 and GE37468 represent a new class of thiopeptide antibiotics with potential therapeutic applications.
- This discovery broadens the scope of EF-Tu as an antibiotic target.