CTXφ Replication Depends on the Histone-Like HU Protein and the UvrD Helicase

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One of the major strategies to prevent Cholera epidemics is the development of oral vaccines based on live attenuated Vibrio cholerae strains. The most promising vaccine strains have been obtained by deletion of the cholera toxin genes, which are harboured in the genome of an integrated phage, CTXϕ. However, they can re-acquire the cholera toxin genes when re-infected by CTXϕ or by hybrid phages between CTXϕ and other vibrio phages, which raised safety concerns about their use. Here, we developed a screening strategy to identify non-essential host factors implicated in CTXϕ replication. We show that the histone-like HU protein and the UvrD helicase are both absolutely required for its replication. We further show that they are essential for the replication of VGJϕ, a representative member of a family of phages that can form hybrids with CTXϕ. Accordingly, we demonstrate that the disruption of the two subunits of HU and/or of UvrD prevents infection of the V. cholerae by CTXϕ and VGJϕ. In addition, we show that it limits CTXϕ horizontal transmission. Taken together, these results indicate that HU- and/or UvrD- cells are promising candidates for the development of safer live attenuated cholera vaccine.

Vyšlo v časopise: CTXφ Replication Depends on the Histone-Like HU Protein and the UvrD Helicase. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005256
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005256

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