Bacteria may possess the solution to their own destruction.
Busting Bacterial Resistance with Bioinformatics
It seems like we're losing the fight against antibiotic-resistant bacteria, a chilling prediction for our future health.
Could Mother Nature have a secret stash of antibiotics waiting for us to discover?
A brand-new study out of The Rockefeller Institute highlights one potential solution: Bioinformatics. This cutting-edge field uses algorithms to sift through microbial genetic data, pinpointing hidden antibiotic agents that could help us outsmart antibiotic resistance.
"We've got a serious problem," said Dr. Cesar de la Fuente-Nunez, from the Perelman School of Medicine at the University of Pennsylvania, summing up the situation. "By 2050, 10 million people could be dying each year from untreatable infections. That's one death every three seconds."
Researchers led by Dr. Sean F. Brady have just published their discovery of a new antibiotic—cilagicin—found using these bioinformatic methods. After testing, cilagicin proved to be highly effective against drug-resistant bacteria, shielding mice from acute infections and showing broad activity against multiple drug-resistant pathogens.
The study's lead author, Dr. Zongqiang Wang, shared the details in Science. Needless to say, Dr. de la Fuente-Nunez wasn't involved in the research.
Embracing the Unseen
Traditional methods of finding antibiotics have relied on lab-grown bacteria producing them via fermentation. But it's often tough to get them to churn out all the antibiotics they're capable of producing.
What if we let computers do the heavy lifting instead?
"Instead of decoding genetic instructions using biological processes, bioinformatic algorithms are used to predict the chemical structures produced by bacteria," explains Dr. Brady. "Then, we synthesize these potential antibiotics."
The molecules responsible for forming these antibiotics are called "synthetic bioinformatic natural products (syn-BNPs)."
With over 10,000 silent, unexplored biosynthetic gene clusters (BCGs) in bacteria, there's immense potential for untapped antibiotics.
Bioinformatics is like the crystal ball that helps us peer into this hidden world, unveiling the secrets that nature has been hiding for millennia.
A New Dawn
The algorithm used by the Rockefeller team zeroed in on BCGs that seemed likely to produce non-ribosomal peptide lipopeptide antibiotics—a class of antibiotics known for inhibiting bacterial growth through multiple modes of action.
One particular cluster, dubbed the "cil" cluster, piqued their interest due to its close relationship with other genes linked to antibiotics from the distant past.
The team tested the cluster using their algorithm and were blown away: It produced cilagicin—a potent new antibiotic that wiped out drug-resistant bacteria, even those specifically bred to resist cilagicin itself.
Best of all, cilagicin was harmless to human cells, and in its drug form, it successfully fought off infections in mice.
Cilagicin's secret weapon? It attacks two vital molecules upon which bacteria depend for maintaining their cell walls. Most antibiotics bind to just one of these molecules, but cilagicin attacks both—leaving drug-resistant bacteria no escape.
Researchers hope that their method for discovering new antibiotics will help buoy us during our drug-resistance crisis. Says Dr. Brady, "Our remaining antibiotic reserve will depend on how carefully we use it. With good stewardship, I'm optimistic that we can prolong their effectiveness long enough for the development of the next generation of antibiotics."
Dr. de la Fuente-Nunez shares this optimism: "I think AI and computers can help us design and discover novel antibiotics. The key is combining machine intelligence with human ingenuity."
- In the face of increasing antibiotic resistance, a new study from The Rockefeller Institute suggests that bioinformatics, a field using algorithms to analyze microbial genetic data, could be a promising solution.
- Given that traditional methods of finding antibiotics have limitations, Dr. Sean F. Brady and his team have discovered a new antibiotic, cilagicin, using bioinformatic methods.
- With more than 10,000 silent, unexplored biosynthetic gene clusters (BCGs) in bacteria, the potential for untapped antibiotics is immense, as revealed by bioinformatics.
- The antibiotic cilagicin, discovered using bioinformatics, has shown remarkable effectiveness against drug-resistant bacteria, attacking two vital molecules that bacteria depend on for their cell walls.
- In the fight against antibiotic resistance, some experts, such as Dr. Cesar de la Fuente-Nunez, believe that combining machine intelligence with human ingenuity through the use of technologies like bioinformatics could lead to the design and discovery of novel antibiotics.
