Targeted antimicrobial therapy in the microbiome era

Abstract

Even though the oral microbiome is one of the most complex sites on the body it is an excellent model for narrow-spectrum antimicrobial therapy. Current research indicates that disruption of the microbiome leads to a dysbiotic environment allowing for the overgrowth of pathogenic species and the onset of oral diseases. The gram-negative colonizer, Porphyromonas gingivalis has long been considered a key player in the initiation of periodontitis and Streptococcus mutans has been linked to dental caries. With antibiotic research still on the decline, new strategies are greatly needed to combat infectious diseases. By targeting key pathogens, it may be possible to treat oral infections while allowing for the recolonization of the beneficial, healthy flora. In this review, we examine unique strategies to specifically target periodontal pathogens and address what is needed for the success of these approaches in the microbiome era.

Keywords: antibiotic resistance; antibiotics; microbiome; oral health; selective drug target.

Figure 1

Evolutionary relationships of oral taxa classified by their essential genes. Oral microbial essential genes were identified by BLAST proteins of completed oral microbial genomes against the Database of Essential Genes (DEG). Candidate essential genes were then manually curated using our essential gene prediction model. Orthologous essential genes were identified among the oral microbial genomes and a phylogenetic tree was built based on the classification of the presence or absence of the essential genes

Figure 2

Targeted antimicrobial treatment to restore the microbial homeostasis. Various factors including manipulation by keystone‐pathogens and changes in diet and other host factors can alter the oral environment leading to changes in the microbial population. The altered environment selects for the growth of certain species, reducing the healthy, microbial diversity. Potential strategies such as the identification of pathogen‐selective essential gene targets, the dispersal of the pathogenic biofilm or the selective delivery of antimicrobial agents could be used to only eliminate the dysbiotic or pathogenic species. This would allow for the re‐establishment of the healthy microbial population and restore homeostasis