Bioinformatic prospecting and synthesis of a bifunctional lipopeptide antibiotic that evades antimicrobial resistance

Good news! Possibly a breakthrough! A new approach to drug discovery and synthesis.

"A new antibiotic, synthesized ... and derived from computer models of bacterial gene products, appears to neutralize even drug-resistant bacteria. The compound, named cilagicin, works well in mice and employs a novel mechanism to attack MRSA, C. diff, and several other deadly pathogens ...

The results suggest that a new generation of antibiotics could be derived from computational models.
“This isn’t just a cool new molecule, it’s a validation of a novel approach to drug discovery,” ... “This study is an example of computational biology, genetic sequencing, and synthetic chemistry coming together to unlock the secrets of bacterial evolution.”...
most antibiotics were first weaponized by bacteria to fight off fellow bacteria. ..."

From the abstract:

"Emerging resistance to currently used antibiotics is a global public health crisis. Because most of the biosynthetic capacity within the bacterial kingdom has remained silent in previous antibiotic discovery efforts, uncharacterized biosynthetic gene clusters found in bacterial genome–sequencing studies remain an appealing source of antibiotics with distinctive modes of action. Here, we report the discovery of a naturally inspired lipopeptide antibiotic called cilagicin, which we chemically synthesized on the basis of a detailed bioinformatic analysis of the cil biosynthetic gene cluster. Cilagicin’s ability to sequester two distinct, indispensable undecaprenyl phosphates used in cell wall biosynthesis, together with the absence of detectable resistance in laboratory tests and among multidrug-resistant clinical isolates, makes it an appealing candidate for combating antibiotic-resistant pathogens."

A synthetic antibiotic may help turn the tide against drug-resistant bacteria

Bioinformatic prospecting and synthesis of a bifunctional lipopeptide antibiotic that evades resistance (no public access)