9-Apr-2018: Odilorhabdins; A new class of antibiotics discovered.

The spread of multidrug-resistant bacteria has prompted a renewed interest in antibiotics with novel chemical scaffolds and mechanisms of action. Scientists describe a previously unknown class of ribosome-targeting antibiotics, Odilorhabdins (ODLs). They reveal the binding site of ODLs in the decoding center of the small ribosomal subunit and show that these inhibitors render the ribosome error prone. Odilorhabdins exhibit bactericidal activity against Gram-positive and Gram negative pathogens and are able to cure bacterial infection in animal models.

• Odilorhabdins are a new class of naturally produced, ribosome-targeting antibiotics.
• ODLs bind to the small ribosomal subunit at a site not exploited by known antibiotics.
• ODLs induce  miscoding, likely by increasing the affinity of aa-tRNAs to the ribosome.
• ODLs show promising antibacterial spectrum and efficacy in mouse infection models.

 Odilorhabdins (ODLs), produced by the enzymes of the non-ribosomal peptide synthetase gene cluster of the nematode-symbiotic bacterium Xenorhabdus nematophila. ODLs show activity against Gram-positive and Gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae, and can eradicate infections in animal models.