Long overlooked as a benign resident of the oral microbiome, Fusobacterium nucleatum has been increasingly linked to cancer progression, metastasis, and chemotherapeutic resistance. Now, researchers have unexpectedly uncovered a compound that may selectively take it out without collateral damage to the broader microbiota.
F. nucleatum, a member of the oral microbiome, can migrate beyond its native niche to colonize the esophageal, colorectal, and breast tissues. Along with its ties to cancer, it has also been associated with other medical conditions such as oral infections, arthritis, and adverse pregnancy outcomes.
While conventional antibiotics can inhibit F. nucleatum and slow tumor progression, their prolonged use disrupts the gut microbiome and contributes to gastrointestinal side effects. Without a targeted approach, broad-spectrum treatments risk triggering dysbiosis and disturbing the body’s microbial balance. Disrupting the gut microbiome can weaken immunity, an especially serious concern for cancer patients and those who are immunocompromised.
Antibiotic-mediated removal of F. nucleatum has been shown to change the course of cancer progression. In a recent study, “An antisense oligomer conjugate with unpredicted bactericidal activity against Fusobacterium nucleatum,” from mBio, researchers at the Helmholtz Institute for RNA-based Infection Research (HIRI) focused on targeted inhibition of F. nucleatum, which could ultimately help with recovery for cancer patients by eliminating these bacteria in carcinomas.
The team initially sought to use antisense oligomers (ASOs)—synthetic molecules that bind to complementary mRNA sequences—to block the production of essential bacterial proteins, potentially paving a path for new possible antibacterial agents.
They focus on one of two popular ASO modalities, peptide nucleic acids (PNAs), a stable, DNA-like ASO with a peptide-mimicking backbone that resists degradation. To enhance bacterial uptake, PNAs were conjugated to cell-penetrating peptides (CPPs), which ferry the cargo across bacterial membranes.
While none of the designed PNAs targeting essential genes impaired bacterial growth, one nontargeting control—FUS79—unexpectedly exhibited potent bactericidal activity against five F. nucleatum strains without interfering with other tested bacterial species. These results suggest that FUS79 might be able to selectively deplete fusobacterial strains from bacterial communities, offering a new perspective on fusobacterial removal at the tumor site. An RNA seq analysis indicated that the combination of FUS79 and the CPP elicited a membrane stress response in vulnerable F. nucleatum strain but not in Fusobacterium nucleatum subsp. vincentii (FNV).
Next steps include unraveling FUS79’s precise mechanism of action and optimizing the compound for enhanced potency. According to Jörg Vogel, PhD, director of HIRI and study co-author, this finding represents an early but promising advance in developing ASO-based antimicrobial strategies. This is the first step toward the design of ASO therapeutics, but appropriate controls are needed for the development of CPP-ASOs as antimicrobial agents. This may be a potential new strategy for more targeted antibiotics and future therapeutics for the wide range of maladies brought on by F. nucleatum.
Read more about other applications of ASOs and their role in drug development here.
The post The Oncomicrobe in the Room: Surprise Antimicrobial Agent Targets <i>F. nucleatum</i> appeared first on GEN - Genetic Engineering and Biotechnology News.
F. nucleatum, a member of the oral microbiome, can migrate beyond its native niche to colonize the esophageal, colorectal, and breast tissues. Along with its ties to cancer, it has also been associated with other medical conditions such as oral infections, arthritis, and adverse pregnancy outcomes.
The trouble with one-size-fits-all antibiotics
While conventional antibiotics can inhibit F. nucleatum and slow tumor progression, their prolonged use disrupts the gut microbiome and contributes to gastrointestinal side effects. Without a targeted approach, broad-spectrum treatments risk triggering dysbiosis and disturbing the body’s microbial balance. Disrupting the gut microbiome can weaken immunity, an especially serious concern for cancer patients and those who are immunocompromised.
Antibiotic-mediated removal of F. nucleatum has been shown to change the course of cancer progression. In a recent study, “An antisense oligomer conjugate with unpredicted bactericidal activity against Fusobacterium nucleatum,” from mBio, researchers at the Helmholtz Institute for RNA-based Infection Research (HIRI) focused on targeted inhibition of F. nucleatum, which could ultimately help with recovery for cancer patients by eliminating these bacteria in carcinomas.
The team initially sought to use antisense oligomers (ASOs)—synthetic molecules that bind to complementary mRNA sequences—to block the production of essential bacterial proteins, potentially paving a path for new possible antibacterial agents.
They focus on one of two popular ASO modalities, peptide nucleic acids (PNAs), a stable, DNA-like ASO with a peptide-mimicking backbone that resists degradation. To enhance bacterial uptake, PNAs were conjugated to cell-penetrating peptides (CPPs), which ferry the cargo across bacterial membranes.
FUS79 and the future of targeted antimicrobials
While none of the designed PNAs targeting essential genes impaired bacterial growth, one nontargeting control—FUS79—unexpectedly exhibited potent bactericidal activity against five F. nucleatum strains without interfering with other tested bacterial species. These results suggest that FUS79 might be able to selectively deplete fusobacterial strains from bacterial communities, offering a new perspective on fusobacterial removal at the tumor site. An RNA seq analysis indicated that the combination of FUS79 and the CPP elicited a membrane stress response in vulnerable F. nucleatum strain but not in Fusobacterium nucleatum subsp. vincentii (FNV).
Next steps include unraveling FUS79’s precise mechanism of action and optimizing the compound for enhanced potency. According to Jörg Vogel, PhD, director of HIRI and study co-author, this finding represents an early but promising advance in developing ASO-based antimicrobial strategies. This is the first step toward the design of ASO therapeutics, but appropriate controls are needed for the development of CPP-ASOs as antimicrobial agents. This may be a potential new strategy for more targeted antibiotics and future therapeutics for the wide range of maladies brought on by F. nucleatum.
Read more about other applications of ASOs and their role in drug development here.
The post The Oncomicrobe in the Room: Surprise Antimicrobial Agent Targets <i>F. nucleatum</i> appeared first on GEN - Genetic Engineering and Biotechnology News.