Fighting Fire with Fire: Phage Potential for the Treatment of E. coli O157 Infection

Abstract

Hemolytic–uremic syndrome is a life-threating disease most often associated with Shiga toxin-producing microorganisms like Escherichia coli (STEC), including E. coli O157:H7. Shiga toxin is encoded by resident prophages present within this bacterium, and both its production and release depend on the induction of Shiga toxin-encoding prophages. Consequently, treatment of STEC infections tend to be largely supportive rather than antibacterial, in part due to concerns about exacerbating such prophage induction. Here we explore STEC O157:H7 prophage induction in vitro as it pertains to phage therapy—the application of bacteriophages as antibacterial agents to treat bacterial infections—to curtail prophage induction events, while also reducing STEC O157:H7 presence. We observed that cultures treated with strictly lytic phages, despite being lysed, produce substantially fewer Shiga toxin-encoding temperate-phage virions than untreated STEC controls. We therefore suggest that phage therapy could have utility as a prophylactic treatment of individuals suspected of having been recently exposed to STEC, especially if prophage induction and by extension Shiga toxin production is not exacerbated.

Phage-specific metabolic reprogramming of virocells

“…Such efforts will require further studying virocells molecularly and biochemically, defining functional guilds, and including both the lytic infection continuum [94] and lysogeny, since it is ubiquitous in nature [60] and can uniquely reprogram cellular metabolisms [95]. Such understanding is critical to inform phage-based applications [96,97] and attain the predictive knowledge needed for modeling phage-host-environment interactions [10].…”

Anti-biofilm and Antibacterial Activity of Allium sativum Against Drug Resistant Shiga-Toxin Producing Escherichia coli (STEC) Isolates from Patient Samples and Food Sources

“…In addition, phytochemical such as essential oils and other phytochemicals are also being evaluated for anti-STEC activity [21,44,45]. Novel alternative treatment options for STEC infections using natural products have been investigated with encouraging results [19]. Recently, derivatization of cationic polysaccharides has been shown to exhibit activity against E. coli [50].…”

“…It has been reported that antibiotic treatment increases Stx production either by releasing intracellular Stx due to lysis or by induction of Stx expression from prophage due to genomic insult caused by antibiotics [16]. Thus, there is a lot of interest in developing novel alternative therapies to treat STEC infection such as antibodies, Stx receptor analogs, novel antibacterial agents, probiotics, phages and plant derived natural products [17][18][19]. The antibacterial activity of Chinese cinnamon, Spanish oregano and savory essential oils against STEC was found to be mediated by compromising the cell wall and membrane [20].…”

The interactions of bacteriophage Ace and Shiga toxin-producingEscherichia coliduring biocontrol

“…Biocontrol strategies using specific bacteriophages (phages) have been proposed as a means to limit EHEC contamination of food products during processing (Anany et al 2011;Coffey et al 2011;Viazis et al 2011;Howard-Varona et al 2018;Son et al 2018) but such measures must be proven safe and efficient. There are two important considerations when selecting new candidate EHEC biocontrol phages.…”