In seeking new antibiotic sources, researchers have turned to an unlikely source: a whiffy frog known as Odorrana andersonii. By unclumping a compound it produces naturally, they’ve found a potential gut-friendly ally in the fight against superbugs.
Frogs aren’t known for living in the cleanest environments. The mud and muck they typically inhabit are crawling with a pretty impressive range of microbes. Yet the amphibians thrive in a huge range of habits over most of the globe and have done so for millions of years. They’ve even survived in the Chernobyl exclusion zone, albeit in a bit darker form.
Therefore, thought an international team of researchers, why not investigate them as a source of drugs to combat the growing trend of antibiotic-resistant bacteria.
So the group turned to Odorrana andersonii, a frog that is most commonly found in South Asia and emits a strong odor to deter predators. By examining the frog’s secretions, the researchers focused on a peptide called Andersonnin-D1 that exhibits antimicrobial action. The issue with the peptide is that it forms clumps when it is secreted, which doesn’t make it a good candidate for clinical use.
To solve this, the researchers used a process called “structure-guided design” in which they made tiny changes to the peptide’s chemical structure until they found a form that resisted clumping and could hold therapeutic promise.
They then tested their new frog-based synthetic peptides on a range of bacteria and found that they were at least as effective as antibiotics such as polymyxin B, which are known as last-resort antibiotics due to their efficacy when other bug-busting drugs have failed. What’s more, the synthetic Andersonnin-D1 didn’t harm human cells in lab tests, nor did it damage beneficial gut bacteria.
The new compound was also found to be effective in combating complex colonies consisting of multiple bacterial species. The peptide was particularly effective against gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. These are some of the bugs that are steadily developing resistance to common antibiotics and are therefore getting difficult to fight.
The researchers plan to continue their preclinical testing and then to submit their peptides for a process known as Investigational New Drug (IND) enabling studies, which would then lead to approval from the US Drug Administration for clinical trials if all goes well.
“We are excited that frogs – and nature in general – can inspire new molecules that could be developed into antibiotics,” said study co-author Cesar de la Fuente, from the University of Pennsylvania School of Engineering and Applied Science. “Thanks to the power of engineering, we can take those natural molecules and turn them into something more useful for humanity.”
The research has been published in the journal Trends in Biotechnology.
Source: University of Pennsylvania via Phys.org