Cholera Bacteriophages: History of Discovery, Structure and Application

Viruses that affect cholera vibrio, or cholera bacteriophages, were discovered in early twentieth century, when the sixth cholera pandemic was raging in Southeast Asia, the Far and Middle East and Europe. This discovery marked the beginning of intensive study of cholera bacteriophages as a promising means in the fight against cholera. The review highlights issues related to the history of the discovery and study of cholera bacteriophages and describes the features of their structure and life cycle. A co-evolutionary strategy for the interaction of cholera bacteriophages with Vibrio cholerae cells, called the “Red Queen dynamics”, is presented. According to this strategy, strains of V. cholerae and cholera bacteriophages, in order to survive, must constantly evolve and adapt, acquiring more and more new systems for defense from each other. The review also provides information about the main currently known anti-phage systems of V. cholerae (mutational changes in the receptor apparatus, release of outer membrane vesicles, restriction-modification system, PLE element, SXT elements, BREX bacteriophage exclusion system and CRISPR/Cas systems, Abi-strategy). Phage counter-defense systems are presented (CRISPR/Cas system, Odn nuclease, epigenetic modification by methylase, BREX countermeasures system). The papaer analyzes the practical application of cholera bacteriophages in the diagnosis of cholera (for identification, determination of the biovar of the pathogen, its virulence and epidemic significance), and outlines the most well-known phage typing schemes. Promising strategies for the use of cholera bacteriophages in phage therapy and phage prevention of cholera are characterized. The effects of combined use of phages and antibiotics in complex therapy are considered separately.