Valentina Cosi

Investigating peptide nucleic acids (PNAs) as antimicrobial agents against Fusobacterium

Valentina Cosi

Helmholt Center for Infections Research - HZI, RABI (HIRI), Inhoffenstraße 7 , 38124 Braunschweig [DE], valentina.cosi@helmholtz-hiri.de

Author(s): Valentina Cosi, Falk Ponath, Chandradhish Ghosh, Jörg Vogel

The oral microbe Fusobacterium nucleatum has gained attention for its ability to colonize tissues as well as tumors distal from its original niche. There fusobacteria can enhance tumor growth, metastasis and resistance to chemotherapy. Removal of the bacteria has been shown to reduce the tumor burden. The aim of this project is to explore the potential of programmable antibiotics in the form of antisense oligomers such as peptide nucleic acid (PNA) to eliminate or modulate fusobacteria.

The antisense PNAs are usually coupled to cell-penetrating peptides (CPPs) for delivery across the bacterial cell wall. In order to determine the most efficient CPP for fusobacteria we examined the uptake of fluorescently labeled CPPs using confocal laser scanning microscopy. Of the tested CPPs (KFF)3K and RXR resulted as the most promising candidates with the highest cytosolic uptake efficiency. The selection of the mRNA target, oligonucleotide length and base composition can also influence the killing capacity of the PNA. We designed PNAs targeting essential genes of F. nucleatum such as acpP, gyrA, and ftsZ. These PNAs showed concentration-depended growth-delay in vitro. To understand the induced translational inhibition and potential downstream effects of PNAs, we plan to use RNA-seq for monitoring global transcriptomic changes. Our final goal is to eradicate fusobacteria at the tumor site using PNAs specifically targeting the oncomicrobe.


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