Tens of thousands die each year from sepsis, which is blood poisoning. Bacteria spread rapidly and damage organ by organ. Then every minute counts. The faster and more specific the treatment, the higher the chances of survival. But there were no new antibiotics against resistant bacteria for a long time. Until now.
Scientists at McMaster University Hamilton in Canada have discovered a new group of antibiotics that kill resistant sepsis bacteria. The study has now been published in the specialist journal “Nature”.
“Coping with the ongoing antibiotic crisis requires the discovery of compounds with novel mechanisms of action that are able to treat drug-resistant infections,” the researchers write. Many antibiotics are obtained from specialized metabolites of bacteria, especially from the Actinomycetes family.
Although actinomycete extracts have traditionally been screened using activity-based platforms, this approach has become unfavorable due to the frequent rediscovery of known compounds. The genome sequencing of actinomycetes would therefore show an untapped reservoir of biosynthetic gene clusters. But prioritization would be required to predict which gene clusters could deliver promising new chemical substances.
“Here we use the phylogeny of the biosynthetic genes along with the lack of known resistance determinants to predict divergent members of the glycopeptide family of antibiotics that are likely to have new biological activities,” it says. And further: “With these predictions, we have discovered two members of a new functional class of glycopeptide antibiotics – the well-known glycopeptide antibiotic Complestatin and a newly discovered compound, which we call Corbomycin – that have a novel mechanism of action.”
The researchers show that by binding to peptidoglycan, complestatin and corbomycin block the action of autolysin – essential peptidoglycan hydrolases that are necessary for the cell wall to transform during growth. Corbomycin and complestatin show little resistance development and are effective in reducing bacterial load in a mouse model of skin MRSA infection.
Now the scientists want to use this approach to discover other antibiotics that work against resistant bacteria.