The Mechanism of Lysis-Lysogeny Decision-Making of Bacteriophage P1
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Date
2021-04-19
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Abstract
Recently, more attention has been raised in regard to the study of bacteria-infecting viruses or bacteriophages for a number of reasons. First, they serve as new weapons against antibiotic-resistant pathogens. In addition, a number of phages, especially temperate phages, have been identified that could help shape bacterial evolution and community composition in the mammalian microbiome, and may influence human health. In virology, temperate refers to the ability of some viruses to choose between alternative modes of propagation, lysis or lysogeny. In the lytic pathway, host cells are killed and new phages are produced; while, in the lysogenic pathway, the virus remains dormant until induction. Coliphage P1 lysogenizes host cells as a low-copy plasmid, and P1-like plasmids have been identified to be prevalent in animal and human pathogens. In order to unveil the role of phage decision-making in virulence dissemination, we investigate the mechanisms underlying P1 lysogenization in comparison with the established paradigm phage λ, using single-cell and single-virus techniques.
First, we examined the influence of early steps in the P1 infection cycle. We found that recognizing the core region of lipopolysaccharides gave P1 the potential of adsorbing at any location on the bacterial cell surface, which ensured a high probability of successful infection in a variety of host bacteria and hence promoted pathogenic spread. Further, it has been reported that P1 exhibits a constant probability of lysogeny regardless of multiplicity of infection (MOI, or the number of phages infecting a cell), which could benefit P1-carried virulent genes maintaining in bacterial hosts. To explore the underlying mechanism, we investigated the expression of P1 regulatory proteins and the interaction between phages infecting the same host. We demonstrated that the constant repression activity of lytic genes for each infecting phage and the ensemble decision made by all infecting phages led to the MOI-independent lysogenic response. Finally, though the probability of an infected cell undergoes lysogeny is consistent over MOIs, factors that bias the final cell outcome is still obscure. In our work, we found that the bacterial cell growth state and different patterns of viral DNA replication exhibited associations with P1 lysis-lysogeny decision-making.
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Decision-making, Bacteriophage P1, gene regulatory circuitry, phage communication, single-cell, fluorescence