Synthetic Antibiotic That Targets Even Drug-Resistant Bacteria Is Uncovered

Here’s a fun fact: despite the most “famous” antibiotic, penicillin, discovered from fungus, the majority of the most potent strains actually originate from bacteria. 

“Eons of evolution have given bacteria unique ways of engaging in warfare and killing other bacteria without their foes developing resistance,” said Sean F Brady, Head of the Laboratory of Genetically Encoded Small Molecules at The Rockefeller University. 

However, as you may have read in recent years, there’s been a rise in the number of antibiotic-resistant bacteria, making it more difficult for researchers to come up with new active compounds to target certain viruses. 

Adding to the challenge is that while most antibiotics are derived from bacteria, many types of bacteria can’t be grown in a laboratory setting. Alternative methods, such as scientists looking for antibacterial genes in soil and cultivating them, aren’t foolproof either. 

Looking for a solution, Brady and his team decided to look into algorithms, by using modern technology to zoom in on genetic instructions within a DNA sequence to predict the structures of antibiotic-like compounds the hypothetical bacterium would produce. 

If a particular test looks promising, organic chemists can then use the data to synthesize the structure within a laboratory, though as with everything in nature, it’s not always perfect. 

“The molecule that we end up with is presumably, but not necessarily, what those genes would produce in nature. We aren’t concerned if it is not exactly right—we only need the synthetic molecule to be close enough that it acts similarly to the compound that evolved in nature,” explained Brady. 

By using this method, postdoctoral associates Zonggiang Wang and Bimal Koirala began an extensive search through the vast genetic-sequence database, happening upon the ‘cil’ gene cluster, which had not been explored previously. 

After feeding the relevant sequences into the algorithm, one of the suggested compounds, dubbed cilagicin, was found to be an active antibiotic. 

In laboratory trials, cilagicin proved to be a ble to reliably kill Gram-positive bacteria without damaging human cells, and even successfully treated bacterial infections in mice. Even better, the antibiotic appeared to work against several drug-resistant bacteria. 

While this is no doubt a significant breakthrough for medicine, you won’t be seeing cilagicin in the pharmacy anytime soon. It’s still a long way’s away from human trials, with scientists having to work on follow-up studies to optimize the compound and determine which diseases it’s most effective in treating. 

The initial findings do signal the untapped potential of how algorithms could be used to discover and develop new, drug-resistant antibiotics on a scale. 

As Brady put it: “This work is a prime example of what could be found hidden within a gene cluster. We think that we can now unlock large numbers of novel natural compounds with this strategy, which we hope will provide an exciting new pool of drug candidates.” 

[via ZME Science and The Rockefeller University / Sci Tech Daily, cover image via Katarzyna Bialasiewicz | Dreamstime.com]