The growing resistance of bacteria to current antibiotics poses a significant threat to public health, pushing the scientific and healthcare communities to find innovative solutions. Enter the Replicate project, led by scientist Ignacio Insua and funded by an ERC Starting Grant.
"Our project proposes a paradigm shift in how antibiotics, and medicines in general, function," explains Insua, a researcher at CiQUS. Instead of administering a traditional molecule like penicillin, the idea is to use two inactive precursors.
But why take a medication that initially does nothing in the body? Insua explains: "These precursors are designed to accumulate in bacteria, which have different nutritional needs than human cells. Once inside, they connect to form an active molecule. This process is self-replicating, meaning the activated antibiotic molecule catalyzes the formation of more, rapidly building up high doses at the infection site."
Early Steps and Future Promise
Insua's team recently published their first paper within this project, titled "Structural Study of Short Amphiphilic Peptides with Autocatalytic Self-Replication." The goal is to identify the smallest structural sequences capable of recognizing each other, a crucial step for self-replication.
Once activated inside bacteria, these molecules act like detergents, dissolving bacterial membranes and making it difficult for bacteria to develop resistance. Traditional antibiotics target specific bacterial components, which, while safe for humans, can lead to resistance due to their specificity.
The Value of Basic Science
Although the concept of molecular self-replication was described in the 1990s, it remained largely unexplored. Insua, with his background in antibiotics, saw its potential. "I realized this could be a game-changer in the field," he says.
Initial proof-of-concept studies demonstrated that certain peptide molecules could achieve the desired effect. With ERC funding, the team can now optimize the system and develop the technology further.
This project underscores the importance of basic science. "You never know when a concept might inspire a technological breakthrough," Insua notes. The multidisciplinary nature of the project, involving chemistry, pharmacology, and nanotechnology, is a testament to CiQUS's collaborative environment.
A Trailblazing Approach
As an innovative and unprecedented project, Replicate faces significant challenges. "There's no existing model for this type of therapy," Insua admits. However, this also presents an opportunity for a paradigm shift in medicine.
"We're not just targeting bacterial infections," Insua explains. "Our work could redefine drug design altogether, with applications extending to cancer and other diseases." By using specific markers, the technology could be adapted to target various cell types, offering a new strategy for smart therapy.
By Laura Veiga, GCiencia.
