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

      Bolocan, Andrei S.; Upadrasta, Aditya; de Almeida Bettio, Pedro H.; Clooney, Adam G.; Draper, Lorraine A.; Ross, R. Paul; Hill, Colin; Science Foundation Ireland; European Union; Janssen Biotech, Inc.; et al. (MDPI, 2019-04-20)
      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.
    • ΦCrAss001 represents the most abundant bacteriophage family in the human gut and infects Bacteroides intestinalis

      Shkoporov, Andrey N.; Khokhlova, Ekaterina V.; Fitzgerald, C. Brian; Stockdale, Stephen R.; Draper, Lorraine A.; Hill, Colin; Ross, R Paul; Science Foundation Ireland; Janssen Biotech, Inc.; SFI/12/RC/2273; et al. (Nature Publishing Group, 2018-11-14)
      CrAssphages are an extensive and ubiquitous family of tailed bacteriophages, predicted to infect bacteria of the order Bacteroidales. Despite being found in ~50% of individuals and representing up to 90% of human gut viromes, members of this viral family have never been isolated in culture and remain understudied. Here, we report the isolation of a CrAssphage (ΦCrAss001) from human faecal material. This bacteriophage infects the human gut symbiont Bacteroides intestinalis, confirming previous in silico predictions of the likely host. DNA sequencing demonstrates that the bacteriophage genome is circular, 102 kb in size, and has unusual structural traits. In addition, electron microscopy confirms that ΦcrAss001 has a podovirus-like morphology. Despite the absence of obvious lysogeny genes, ΦcrAss001 replicates in a way that does not disrupt proliferation of the host bacterium, and is able to maintain itself in continuous host culture during several weeks.