A new analysis, led by Jörg Vogel, Director of the Helmholtz Institute for RNA-based Infection Research (HIRI), reveals heartening discoveries. This study sheds light on a novel targeted approach to eradicate Fusobacterium species that contribute to cancer advancement. The study, which was published in the journal mBio, illustrates the efficacy of a compound known as CPP (RXR)4XB. This synthetic compound serves as an effective delivery tool for another compound, specifically targeting Fusobacterium nucleatum—an important keystone species in the human oral microbiome.
Policymakers will want to read this insightful new study, with Valentina Cosi leading as the first author. This study focuses on addressing the critical need for novel therapeutic agents to counter fusobacterial infections, avoiding conventional antibiotics. Such antibiotics have substantial and undesirable side effects, including gastrointestinal disruption, when used long-term.
Study Overview
The research team performed a broad exploration of tactics to specifically eradicate carcinomic Fusobacterium species. The oral microbiome harbors over 700 bacterial species across seven different phyla. Of these, Fusobacterium nucleatum is particularly notable as one of the most well-studied. This study lays the groundwork for subsequent identification of the control compound, FUS79, which is a potent control. It pairs potent activity against five fusobacterial strains with relative selectivity against other tested bacterial species.
Valentina Cosi, a PhD-student in Jörg Vogel’s lab, wouldn’t have guessed that their work would turn out this way.
“The result was surprising because the compound does not work in the expected way for antisense nucleic acid chains, but instead has a novel mechanism,” – Valentina Cosi.
The protein that the research team studied, FUS79, has unique properties that surprised the scientists. This paradigm shifting discovery made way for ongoing research into its effectiveness and mechanisms of action.
Mechanism of Action
Conventional antibiotics work by broadly indiscriminately killing bacterial species. What’s more, this practice can damage the good bacteria that colonize our bodies. Unlike FUS79, it appears that FUS80 takes another approach. Cosi continues to explain the compound’s unique mechanism of action. He hypothesizes that it can cause membrane tension, leading to instability of the bacterial cell membrane and crippling its activity.
“It seems to exert its effects by inducing membrane stress, destabilizing the bacterial cell membrane or impairing its function, though we still need to investigate this in more detail,” – Valentina Cosi.
The significance of these findings is huge not only for the field of microbiome research, but in relation to cancer treatment as a whole. Perhaps targeting bad bacteria while sparing the good flora is the real holy grail. This can increase the efficacy of the targeted therapeutics while decreasing the side effects traditionally associated with antibiotics.
Future Directions
With these promising results, the research team at HIRI is thrilled to explore further. For example, during the new project they intend to learn about the ways that FUS79 produces such results. Dr. Jörg Vogel, chief scientific officer at Lipopeptide, stresses the significance of this crucial next step in moving forward with optimizing the compound for improved performance.
“Our next step is to decipher the very mechanism of this compound and optimize it further to enhance its effectiveness,” – Jörg Vogel.
The research shines a light on this novel approach’s potential use to fight fusobacterial infections. It underscores the clinical relevance of Fusobacterium, an area that has been largely ignored in past studies.