Abstract
Bacteriophage or phage therapy involves using phages or their products as bio-agents for the treatment or prophylaxis of bacterial infections or diseases. Bacteriophages have the ability to regulate the oral microflora by lysing sensitive bacterial cells and releasing bacterial components with pro-inflammatory activity. Bacteriophages carry specific polysaccharide depolymerases that aid viral penetration and can disrupt the pathogenic process associated with biofilm and exopolysaccharide in the oral cavity. Oral diseases are mainly caused by biofilm forming microorganisms and phages are now being used for biocontrol of oral biofilms. Phages for Actinomyces species, Aggregatibacter actinomycetemcomitans, Enterococcus faecalis, Fusobacterium nucleatum, Lactobacillus species, Neisseria species, Streptococcus species, and Veillonella species have been isolated and characterized. Bacteriophages could be considered as potential therapeutic tools for the elimination of caries, periodontitis, and other diseases of the oral cavity.
Keywords
- oral microbiome
- oral phages
- oral biofilms
- oral diseases
- bacteriophage therapy
1. Introduction
Bacteriophages are viruses that attack bacteria. Phages are now known to cure antibiotic-resistant bacterial infections as well as decrease bacterial virulence by overcoming the barriers bacteria used to avoid them. Bacteriophages are now being explored as potential therapeutic tools for the elimination of oral bacterial pathogens. Bacteriophages can disrupt pathogenic processes associated with biofilm and exopolysaccharide formation by oral microflora. Bacteriophages are a habitat to the human oral cavity where the oral pathogenic bacteria exist. Earlier studies show the isolation of oral bacteriophage from the oral cavity when an oral bacteriophage infecting
2. Actinomyces bacteriophages
Actinomyces species are found in healthy mouth but are also implicated in oral abcesses and oral-facial actinomycosis. Actinomyces, together with streptococci, initiates the biofilm development and formation of dental plaque [8]. Bacteriophages are used to block this co-aggregation to reduce the biofilm development without reducing health-related Actinomyces, which is part of the oral microbiome. The most commonly studied Actinomyces phage was AV-1, but it had a very narrow host range [9]. However, when the phage AV-1 was combined with AV-11, they lysed most of the indicator strains used for Actinomyces studies [10]. Actinomyces phages probably use surface structures of streptococci as receptors. These phages are from the families’ Siphoviridae (61%) and Podaviridae (11%) [11, 12].
3. Aggregatibacter bacteriophages
Aggregatibacter is the causative agent of localized aggressive periodontitis. Aggregatibacter phages are mostly temperate phages and easy to isolate. Engineered Aggregatibacter bacteriophages that release biofilm degrading enzymes like dispersion B to breakdown biofilm have been used against periodontitis causing
4. Enterococcus bacteriophages
5. Streptococcus bacteriophages
The most important species that play a key role in dental plaque formation are oral Streptococci. The oral streptococci mainly constitute 12 species including
6. Bacteriophages for oral anaerobes
6.1 Fusobacterium bacteriophages
6.2 Porphyromonas, prevotella, and tannerella
Prevotella phages have been detected
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
6.4 Veillonella phages
It is a non-motile gram-negative diplococci.
6.5 Lactobacillus
Bacteriophages for the caries associated with 12 strains of Lactobacillus including
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
7.2 Bacteriophages in oral diseases
Bacteriophages are being isolated to bacteria causing oral infections. Bacteriophages have been isolated to both aerobic and anaerobic microorganisms associated with periodontitis. Bacteriophages also constitute the majority of periodontal viral communities [42]. This variation in bacteriophages in healthy and periodontitis patients suggests a potential for more bacteriophage exploration. The use of bacteriophages has also been done in root canal treatment but targeted mainly against
7.3 Bacteriophages as antibiotic adjuvants
Phages can be used as adjuvants to antibiotic therapy. Resistance developed in phages can be reduced by using a cocktail of phages or phage recombinant lysins. Now, genetically engineered phages have also been developed to tackle resistance strains [45, 46].
The use of strictly lytic phages that infect only the target bacteria without affecting the normal microflora can be used as an alternative to local or systemic antibiotic therapy. This phage-based treatment can be designed in each case favoring personalized medicine.
8. Conclusion
The oral diseases caries, periodontal diseases, periapical and endodontic lesions, perimplantitis, and oral mucosal infections are microbial in origin. Bacteriophages are useful candidates for these biofilm-mediated diseases. As antibiotic resistance has become a matter of global concern, the bacteriophages or phage therapy can be used particularly to reduce the impact of acute infections. Moreover, antibiotics have a limited effect on the biofilm and are not much useful for the treatment of oral diseases. However, few bacteriophages are not effective against degrading biofilms; therefore, enzymatic or engineered phages are being investigated. Phages are low in cost, easy to isolate, and efficient against biofilm, and are bacteria specific. Phages have a great potential to be used in the prevention, control, and therapeutics of oral infections.
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