Phages of life – the path to pharma

Abstract

*Equal contribution.Bacteriophage (phage) therapy has encountered both enthusiasm and scepticism in the past century. New antimicrobial strategies against lethal pathogens are now a top priority for the World Health Organization, and although compassionate use of phages recently met with significant success, regulated clinical interventions seem unlikely in the near future. The hundredth anniversary of their discovery seems an appropriate time for a revival of phage therapy, particularly as the dilemma of antibiotic resistance grows. Phages are ubiquitous in the environment, on our food and in and on our bodies. Their influence on human health is currently being evaluated, and in this mini-review, we examine data from recent metagenomic studies that propose a role for phages in the structure of the microbiome and in health and disease. We assess evidence for phages as vehicles for gene transfer in the context of antibiotic resistance and discuss challenges and opportunities along the critical path from phage discovery to a patient-focused pharmaceutical intervention.

Gut Reactions: Breaking Down Xenobiotic–Microbiome Interactions

“…Meanwhile, nextgeneration probiotics may be based on the use of microbes found to be deficient in certain disorders, as is the case of A. muciniphila in obesity, diabetes, and cardiometabolic diseases (Cani and de Vos, 2017), or Faecalibacterium prausnitzii in IBD if the positive preclinical results in models of colitis successfully translate to the clinic (O'Toole et al, 2017). Pathogen-specific antimicrobials and the development of bacteriocins as alternative therapeutic options is another avenue under exploration (Maxson and Mitchell, 2016;Mathur et al, 2017;Munguia and Nizet, 2017), as is the potential use of bacteriophage (Forde and Hill, 2017). Precision editing of the gut microbiota may also be possible, with an example being the use of tungstate treatment to selectively inhibit microbial respiratory pathways, which are operational specifically during episodes of localized gut inflammation (Zhu et al, 2018).…”

Development of a Bacteriophage Cocktail to Constrain the Emergence of Phage-Resistant Pseudomonas aeruginosa

“…Moreover, P. aeruginosa strains are frequently resistant to multiple classes of antibiotics (Lopez-Causape et al, 2018), and P. aeruginosa is a member of the ESKAPE pathogens (Boucher et al, 2009), which include six pathogens with well-recognized abilities to develop antibiotic resistance and cause deadly clinical outbreaks. With the emergence of multidrug-resistant isolates of P. aeruginosa (Sun et al, 2013;Lopez-Causape et al, 2018), phage therapy has received renewed attention (Forde and Hill, 2018;Jault et al, 2018;Kortright et al, 2019), and is a promising alternative approach for treating recalcitrant P. aeruginosa infections (Roach et al, 2017;Waters et al, 2017;Forti et al, 2018;Jault et al, 2018).…”

Potential Application of Bacteriophages in Enrichment Culture for Improved PrenatalStreptococcus agalactiaeScreening

“…Hence, the calculated cost of phage mixture per assay in the current study is only $2.2 × 10 -7 ($4.4 × 10 -13 /phage particle multiplied by the number of phage particles in the mixture, i.e., 1.0 × 10 7 PFU/ml × 50 μl). Several commercial phage companies have been founded worldwide (38). Thus, phage mixture may, in theory, be produced for the S. agalactiae culture test in a cost-effective manner.…”