**6.1 Fusobacterium bacteriophages**

*Fusobacterium nucleatum* bacteriophages have been isolated from saliva samples [31]. Siphovirus Fnpϕ02 could target three subspecies of *F. nucleatum*, *F. vincentii*, and *F. polymorphum*. The second phage Fnpϕ02 was rapidly absorbed on the cell surface but slow lysis was observed. In another study, non-infective phages were obtained by mitomycin C treatment of *F. nucleatum* [32]. The full-genome sequence and functional characterization of a novel lytic bacteriophage FNu1 against *F. nucleatum* which can break down oral biofilms have been reported recently [33].

### **6.2 Porphyromonas, prevotella, and tannerella**

Prevotella phages have been detected *in vivo* [34]. Phages against *Porphyromonas gingivalis* and *Tannerella forsythia* have not been isolated so far. *P. gingivalis* that is an important anaerobic periodontal pathogen-causing microbial dysbiosis may protect itself in the periodontal pockets where many bacteriophages are preset by CRISPR-CAS systems providing it adaptive immunity [35]. These CRISPR-CAS systems are the only adaptive immune system in bacteria to fight phages/viruses, plasmids, transposons, integrative conjugative elements and are also found to target undesirable bacteria in the microbiome. On invasion or exposure to foreign DNA, the spacer sequences are transcribed into small CRISPR RNAs used by Cas proteins to cleave foreign DNA thus acquiring "acquired memory" of this adaptive immune system.

### **6.3 Treponema**

A single study has reported the isolation of Treponema phage [36]. Phage ϕtd1 that belongs to Myoviridae family was harvested from the biofilm culture of *T. denticola* and its genome was detected by polymerase chain reaction.

### **6.4** *Veillonella* **phages**

It is a non-motile gram-negative diplococci. *Veillonella* is a part of the normal flora of the mouth is also associated with oral infections. Around 25 *Veillonella* phages have been isolated from mouth wash specimens. The small plaque-forming was found to be active against *Veillonella rodentium*. The large plaque formers were active against clinical *Veillonella* spp. isolates. Virion morphology was studied only for functional phages N2, N11, and N20 [37].

### **6.5 Lactobacillus**

Bacteriophages for the caries associated with 12 strains of Lactobacillus including *L. casei* have been isolated. They have been divided into two groups: PL-1 is a lytic phage and temperate phage phi FSW of *L. casie* ATCC27139 [38].

### **7. Uses of oral bacteriophages**

### **7.1 Bacteriophages and oral biofilms**

The effectiveness of oral bacteriophages has been mainly seen by the reduction in the count of viable bacteria in the oral biofilms by using them. However, the phages were not able to reduce the amount of extracellular matrix in the biofilms [39]. Another factor while using phages is the phage therapy will be partially effective if particularly if the biofilm is old. The penetration and effect of phages on multispecies oral biofilms has also not been much studied. In a study in two species of biofilm constituting of phage-resistant and phage-susceptible bacteria, it was seen that the species composition of the biofilm may modulate phage effectiveness [40]. Limited studies show the application of oral phages *in vivo* using animal models. The efficacy of oral phages formulated in thermo-sustained release system against *E. faecalis* has been studied *in vivo* using a rat model. The study showed that per-apical inflammation of the tooth was improved after phage treatment [41].
