Reviving Phage Therapy for the Treatment of Cholera

Abstract

Cholera remains a major risk in developing countries, particularly after natural or manmade disasters. Vibrio cholerae El Tor is the most important cause of these outbreaks, and is becoming increasingly resistant to antibiotics, so alternative therapies are urgently needed. In this study, a single bacteriophage, Phi_1, was used prophylactically and therapeutically to control cholera in an infant rabbit model. In both cases, phage-treated animals showed no clinical signs of disease, compared with 69% of untreated control animals. Bacterial counts in the intestines of phage-treated animals were reduced by up to 4 Log10 CFU/g. There was evidence of phage multiplication only in animals which received a V. cholerae challenge. No phage-resistant bacterial mutants were isolated from the animals, despite extensive searching. This is the first evidence that a single phage could be effective in the treatment of cholera, without detectable levels of resistance. Clinical trials in human patients should be considered.

Review article: bacteriophages in gastroenterology—from biology to clinical applications

“…Due to rapid symptom development and the role of cholera toxin in the clinical syndrome, phage therapy might not be useful as a treatment for patients with symptomatic infections, although it may be used to control the spread of the disease such as prophylaxis for high‐risk individuals during an outbreak . Nevertheless, pre‐clinical data suggest that phage therapy may be used with therapeutic or prophylactic intent …”

The Gordon Memorial Lecture: novel approaches to controlling bacterial infections

“…In the case of human cholera, there is the opportunity for breaking this cycle through treatment in hospitals or clinics where the faeces of the infected and treated individuals can be collected and composted. We and others have shown that lytic phage can be highly effective and reducing V. cholerae numbers in the gut and associated clinical signs using experimental animal infections (Bhandare et al 2018).…”

Predatory bacteria as living antibiotics – where are we now?

“…As such, the replication of both B. bacteriovorus and phage may be subject to a minimum host/prey threshold, below which they cannot sustain their populations indefinitely. However, this may be therapeutically beneficial as elimination of a pathogen is often not necessary to achieve significant reductions or complete resolution of disease symptoms [63,94]. The host range of an individual phage is usually restricted to a number of strains within a species or one or two closely related species of bacteria, which makes the maintenance of their populations more challenging than B. bacteriovorus.…”