Browsing School, Graduate by Subject "Bacteriophage T4--immunology"
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Setting the phage for evolution: The mechanism of host exclusion of bacteriophage T4IPI-The interaction of bacteria and their bacteriophages (phages) has led to the evolution of a variety of phage exclusion systems, which has in turn aggravated the realization of cognate exclusion avoidance mechanisms. Chief among these exclusionary entities are restriction-modification (RMS) and modification-dependent system (MDS) enzymes that function to modify and/or digest the invading phage DNA. To combat these enzymes, phages employ various strategies including DNA modification and protein-based interference. The T-even phages of Myoviridae utilize extended DNA modifications to evade host RMS's, inclusive of adenine and cytosine methylation, hydroxymethylation of cytosine (HMC) and further alpha- and beta glucosylation of HMC derivatives (glc-HMC) of targeted sites. Prior to the discovery of an E. coli K isolate, CT596, capable of halting infection by T4 phage lacking the encapsidated IPI* protein (T4IPI-), no restriction system was known able to exclude this glc-HMC DNA phage. It was shown that the affecter exclusion genes gibegs (36.649 kb) and gibegd (26.854 kb) are encoded in a cryptic prophage element within CT596 and are both necessary and sufficient to confer upon a host cell the ability to restrict infection by T4IPI- phage. It was speculated that IPI*, and the evolution of the highly diverse and expanded capsid-targeted internal protein 1 (IP1) locus genes by the glc-HMC T-even family of phages, was for the specific purpose of inhibiting the action of an exclusion system. Discovery of gibegs and gibegd has provided evidence that the IPI* protein and the IP1 locus gene products are directly involved in determining the host range of the individual T-evens.