Since the first accidental discovery of penicillin by Alexander Fleming in 1928 [1], the use of antibiotics has revolutionized healthcare and contributed to saving numerous lives worldwide. Over the years, several molecules have been developed to act in a similar capacity, and their use has been generalized beyond hospitals, making its ways into farming, research and veterinary medicine [2].

Despite their many benefits, the widespread use of antibiotics has led to a new, complex problem : antibiotic resistance. This is far from a small problem. In 2019, 1.27 million people died as a direct result from complications of antibiotic-resistant infections [3].

Given this reality, it’s clear that bacteria are incredibly good at defending themselves. They have developed an impressive set of strategies to fight off antibiotics and render them ineffective. Most notably, these include the alteration of permeability/sequestration, the modification or destruction of the antibiotic, and the modification or replacement of the antibiotic’s target. On top of that, bacteria can share their resistance genes with one another, through several mechanisms at their disposal. Altogether, this arsenal of defenses makes antibiotic resistance one of the major public health challenges of our time [4].

In response to the acquisition of new resistance genes, researchers are compelled to develop new antibiotics, either by modifying existing molecules or by designing novel compounds that target different bacterial processes. This dynamic creates a continuous arms race between bacteria and healthcare professionals: the former evolving new resistances, while the latter strive to counter them with new therapeutic agents. Unfortunately, this race increasingly appears to favor the bacteria, as they acquire resistance faster than we can develop effective countermeasures, rendering many of our current therapeutic options progressively less effective.

Continuing this fight using traditional approaches is therefore doomed in the long term. A new strategy to combat bacterial infections, one that leverages the vast body of existing research, is thus urgently needed. This naturally leads to the question: is there an alternative strategy capable of eradicating bacteria rapidly and efficiently? Moreover, can we achieve this without the bacteria even detecting that they are under attack in the first place?

Concept From myth to science...?

For those unfamiliar with Greek mythology, the Trojan Horse was a massive wooden structure presented to the Trojans by the Greeks during the Trojan War. Mistaking it for a symbol of victory, the Trojans brought it inside the city walls, unaware of the danger it concealed. Hidden within the horse were Greek soldiers, who, under the cover of night, emerged from the structure and opened the gates to the rest of their army, leading to the city’s destruction and ultimately ending the war [5].

Although this story is merely a myth, the project Totally [Fe]rocious aims to repurpose the clever strategy of the Greeks, except this time on the nanoscale. In our battle, the siderophore aerobactin acts as the "Trojan horse", while gold nanoparticles act as the "soldiers" it delivers to infiltrate K. pneumonia, our "Troy".

Feel free to look into our different pages and learn more about our project!