RstB2 Protein, the DNA Binding Protein of CTXΦ Phage from V. cholerae: Current Status and Pending Research

Cholera is a preventable and easily treatable disease that has been eliminated in industrialized countries but is still present in Africa, Southeast Asia, and currently, it was spread in the Latin America and Caribbean region. It requires immediate treatment because it can cause death within hours, even in previously healthy people. Cholera is caused by infection of the intestine with the Gram-negative bacterium Vibrio cholerae which acquires the virulence factor via lysogenic conversion by a filamentous phage, CTXΦ carrying the cholera toxin genes [1]. This unusual lysogenic filamentous phage can either replicate as a plasmid in the absence of the CTXΦ chromosome integration site or sitespecifically integrate into Vibrio cholerae chromosomes [1,2]. Lysogenic conversion results from the exchange of a single pair of strands between attachment site on the genome and the bacterial chromosome of one or the other of the two circular chromosomes of V. cholerae, which is catalysed by the XerCD recombinases [3-5]. The mechanism of CTXΦ integration into the V. Cholerae chromosome has been widely investigated [3-8]. It has been proven that integration is catalyzed by recombinases encoded by XerCD genes [6], using as a substrate the genomic ssDNA of the phage for recombination with the bacterial chromosomal dif1 site [6]. The genomic ssDNA must fold into stem-loop structure, creating a small region of duplex DNA that is target of the sitespecific recombinases [2]. Like the tyrosine recombinases, the phage-encoded protein RstB and some phage-encoded and hostencoded factors are required for CTXΦintegration [3,9]. Among host-encoded factors, it was found that some of the host proteins determine the catalytic state of the Xer recombinases [10,11]. This recombination generates either a single CTXΦ prophage or tandem prophages, which can serve as a template for production of extra chromosomal phage DNA. Unlike other phage sitespecific integration mechanisms, CTXφ integration is irreversible [3]. RstB2 Protein, the DNA Binding Protein of CTXΦ Phage from V. cholerae: Current Status and Pending Research