Evaluation of Phage Therapy in the Context of Enterococcus faecalis and Its Associated Diseases

Abstract

Bacteriophages (phages) or bacterial viruses have been proposed as natural antimicrobial agents to fight against antibiotic-resistant bacteria associated with human infections. Enterococcus faecalis is a gut commensal, which is occasionally found in the mouth and vaginal tract, and does not usually cause clinical problems. However, it can spread to other areas of the body and cause life-threatening infections, such as septicemia, endocarditis, or meningitis, in immunocompromised hosts. Although E. faecalis phage cocktails are not commercially available within the EU or USA, there is an accumulated evidence from in vitro and in vivo studies that have shown phage efficacy, which supports the idea of applying phage therapy to overcome infections associated with E. faecalis. In this review, we discuss the potency of bacteriophages in controlling E. faecalis, in both in vitro and in vivo scenarios. E. faecalis associated bacteriophages were compared at the genome level and an attempt was made to categorize phages with respect to their suitability for therapeutic application, using orthocluster analysis. In addition, E. faecalis phages have been examined for the presence of antibiotic-resistant genes, to ensure their safe use in clinical conditions. Finally, the domain architecture of E. faecalis phage-encoded endolysins are discussed.

Keywords: E. faecalis; OrthoMCL; phage therapy.

Figure 1

Genomic comparison of Enterococcus phages. (A) Neighbor-joining tree based on the percentage of shared orthologous genes (1000 bootstrap replicates); squares indicate the 10 phage putative orthoclusters. (B) Dot plot comparison of amino acids identity among the 10 orthoclusters; genes that share more than 40% homology were considered as being part of the same orthologous group. The vertical axis shows phage clusters and phage IDs.

Figure 2

Maximum likelihood phylogenetic analysis sequence relatedness of the Enterococcus faecalis phage putative metallo-beta-lactamase gene (orthologous group 32); tree node labels represent bootstrap values.

Figure 3

Maximum likelihood phylogenetic analysis sequence relatedness of E. faecalis phage endolysin functional domains; tree node labels represent the bootstrap values; the sequence similarity between functional domains is evidenced by using identical filling patterns; in blue—active domain; in orange—biding in domain; each of the four orthologous group is represented by a different color; Ef62phi could not be associated to any orthologous group.