In Vitro and In Vivo Bacteriolytic Activities of Escherichia coli Phages: Implications for Phage Therapy

Abstract

Four T4-like coliphages with broad host ranges for diarrhea-associated Escherichia coli serotypes were isolated from stool specimens from pediatric diarrhea patients and from environmental water samples. All four phages showed a highly efficient gastrointestinal passage in adult mice when added to drinking water. Viable phages were recovered from the feces in a dose-dependent way. The minimal oral dose for consistent fecal recovery was as low as 10 3 PFU of phage per ml of drinking water. In conventional mice, the orally applied phage remained restricted to the gut lumen, and as expected for a noninvasive phage, no histopathological changes of the gut mucosa were detected in the phage-exposed animals. E. coli strains recently introduced into the intestines of conventional mice and traced as ampicillin-resistant colonies were efficiently lysed in vivo by phage added to the drinking water. Likewise, an in vitro phage-susceptible E. coli strain freshly inoculated into axenic mice was lysed in vivo by an orally applied phage, while an in vitro-resistant E. coli strain was not lysed. In contrast, the normal E. coli gut flora of conventional mice was only minimally affected by oral phage application despite the fact that in vitro the majority of the murine intestinal E. coli colonies were susceptible to the given phage cocktail. Apparently, the resident E. coli gut flora is physically or physiologically protected against phage infection.

Prevalence of Staphylococcus aureus and Lack of Its Lytic Bacteriophages in the Anterior Nares of Patients and Healthcare Workers at a Rural Clinic

“…The CM&R 2011 : 2 (June) Anterior nares, S. aureus and lytic phages reported incidence rate of S. aureus in the anterior nares is 28% to 32%, 2,28 and reported prevalence of lytic bacteriophages in certain niches on the human body ranges from 3% to 33%. [19][20][21] With a 30% S. aureus carriage rate and a phage prevalence range of 3% to 33%, we estimated that the likelihood of detecting at least one phage in 202 samples would be 1 -(1 -.3 × .03) 202 = 84% (lower estimate), and 1 -(1 -.3 × .3) 202 = 99% (upper estimate).…”

“…), with estimates ranging from 10 30 to 10 32 in total, and they play key roles in regulating the microbial balance in every ecosystem where this has been explored. 18 Lytic bacteriophages against different bacterial species have been isolated and even suggested to be part of the complex microbiome of the human gut, 19,20 oral cavity, 21,22 and vagina. 23 The lytic phages are likely to modulate the rate of prevalence for one or more bacteria in different microbiological niches in the body.…”

Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters

“…The complexities and dynamics of the mucus layer are rarely considered, and the activity of phages therein is mostly unknown. Not surprisingly, phages effective in vitro do not consistently reduce mucosal bacterial host levels in vivo (6,7). An understanding of the interactions between phages and their bacterial hosts within the relevant physiological environment is critical for consistent success of phage therapy applications.…”

The complete genomes and proteomes of 27 Staphylococcus aureus bacteriophages

“…Lytic bacteriophages have shown clinical promise as therapeutic agents for topical or systemic treatments of bacterial infections (11) or for their ability to block and subvert essential host metabolic pathways (12). The latter point makes them attractive tools to discover and validate essential bacterial genes targeted during the phage replicative cycle.…”