Abstract
Fusobacterium nucleatum is an important oral bacterium that has been linked to the development of chronic diseases such as periodontitis and colorectal cancer. In periodontal disease, F. nucleatum forms the backbone of the polymicrobial biofilm and in colorectal cancer is implicated in aetiology, metastasis and chemotherapy resistance. The control of this bacteria may be important in assisting treatment of these diseases. With increased rates of antibiotic resistance globally, there is need for development of alternatives such as bacteriophages, which may complement existing therapies. Here we describe the morphology, genomics and functional characteristics of FNU1, a novel bacteriophage lytic against F. nucleatum. Transmission electron microscopy revealed FNU1 to be a large Siphoviridae virus with capsid diameter of 88 nm and tail of approximately 310 nm in length. Its genome was 130914 bp, with six tRNAs, and 8% of its ORFs encoding putative defence genes. FNU1 was able to kill cells within and significantly reduce F. nucleatum biofilm mass. The identification and characterisation of this bacteriophage will enable new possibilities for the treatment and prevention of F. nucleatum associated diseases to be explored.
Highlights
Fusobacterium nucleatum is a Gram-negative facultative anaerobic bacillus that is a normal component of the oral microbiome
The novel bacteriophage FNU1 genome is over 130 kb in length and displays little homology to other known viral genomes
FNU1 has almost 8% of its open reading frames (ORFs) devoted to putative defence against bacterial anti-bacteriophage systems, with several genes each coding for putative antirepressors, methylation genes to avoid restriction modification and toxin-antitoxin mechanisms that may prevent abortive infections
Summary
Fusobacterium nucleatum is a Gram-negative facultative anaerobic bacillus that is a normal component of the oral microbiome It has been associated with periodontal diseases as well as malignancies of the oral cavity, head and neck, oesophagus, cervix, stomach and colon. F. nucleatum has been shown to act as a backbone for pathogenic subgingival polymicrobial biofilms by forming a bridge between the more commensal early colonisers and the more pathogenic late colonisers1,7,8 This microbial biofilm is responsible for the initiation and progression of chronic periodontitis. Current treatment of colorectal cancer includes surgery, chemotherapy and radiation therapy In both cases, a targeted therapy that attacks Fusobacterium in biofilms can potentially provide a new modality to combat these important diseases. C. acnes has been isolated frequently with F. nucleatum but no bacteriophages have been found that target both F. nucleatum and C. acnes
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