Vibrio Phage VMJ710 Can Prevent and Treat Disease Caused by Pathogenic MDR V. cholerae O1 in an Infant Mouse Model

Abstract

Cholera, a disease of antiquity, is still festering in developing countries that lack safe drinking water and sewage disposal. Vibrio cholerae, the causative agent of cholera, has developed multi-drug resistance to many antimicrobial agents. In aquatic habitats, phages are known to influence the occurrence and dispersion of pathogenic V. cholerae. We isolated Vibrio phage VMJ710 from a community sewage water sample of Manimajra, Chandigarh, in 2015 during an outbreak of cholera. It lysed 46% of multidrug-resistant V. cholerae O1 strains. It had significantly reduced the bacterial density within the first 4–6 h of treatment at the three multiplicity of infection (MOI 0.01, 0.1, and 1.0) values used. No bacterial resistance was observed against phage VMJ710 for 20 h in the time–kill assay. It is nearest to an ICP1 phage, i.e., Vibrio phage ICP1_2012 (MH310936.1), belonging to the class Caudoviricetes. ICP1 phages have been the dominant bacteriophages found in cholera patients’ stools since 2001. Comparative genome analysis of phage VMJ710 and related phages indicated a high level of genetic conservation. The phage was stable over a wide range of temperatures and pH, which will be an advantage for applications in different environmental settings. The phage VMJ710 showed a reduction in biofilm mass growth, bacterial dispersal, and a clear disruption of bacterial biofilm structure. We further tested the phage VMJ710 for its potential therapeutic and prophylactic properties using infant BALB/c mice. Bacterial counts were reduced significantly when phages were administered before and after the challenge of orogastric inoculation with V. cholerae serotype O1. A comprehensive whole genome study revealed no indication of lysogenic genes, genes associated with possible virulence factors, or antibiotic resistance. Based on all these properties, phage VMJ710 can be a suitable candidate for oral phage administration and could be a viable method of combatting cholera infection caused by MDR V. cholerae pathogenic strains.

Cholera rages in Africa and the Middle East: A narrative review on challenges and solutions

“…Additionally, they demonstrated that when given 6–12 h before the bacterial challenge, the phage VMJ710 can prevent the progression of V. cholerae infection and ailment. This phage could be a good choice for oral delivery and could help treat cholera infections brought on by pathogenic multidrug‐resistant V. cholerae strains 205 . Another promising cure for cholera is probiotics.…”

“…This phage could be a good choice for oral delivery and could help treat cholera infections brought on by pathogenic multidrug‐resistant V. cholerae strains. 205 Another promising cure for cholera is probiotics. The goal of probiotic treatment for cholera infection is to bring back balance to the gut bacteria and stop V. cholerae strains from taking over the digestive system.…”

Characterization and Anti-Biofilm Activity of Lytic Enterococcus Phage vB_Efs8_KEN04 against Clinical Isolates of Multidrug-Resistant Enterococcus faecalis in Kenya

“…The EOP was calculated by dividing the average plaque-forming units (PFU) of the test bacteria by the average PFU of the host bacteria. Phages were categorized as high production (EOP ≥ 0.5) when the productive infection on the test bacteria resulted in at least 50% of the PFU found for the primary host; medium production (0.1 ≤ EOP < 0.5); low production efficiency (0.001 <EOP< 0.1); inefficient (EOP ≤ 0.001), and reference (EOP = 1) [33,34].…”