Abstract
BackgroundBecause biotechnological uses of bacteriophage gene products as alternatives to conventional antibiotics will require a thorough understanding of their genomic context, we sequenced and analyzed the genomes of four closely related phages isolated from Clostridium perfringens, an important agricultural and human pathogen.ResultsPhage whole-genome tetra-nucleotide signatures and proteomic tree topologies correlated closely with host phylogeny. Comparisons of our phage genomes to 26 others revealed three shared COGs; of particular interest within this core genome was an endolysin (PF01520, an N-acetylmuramoyl-L-alanine amidase) and a holin (PF04531). Comparative analyses of the evolutionary history and genomic context of these common phage proteins revealed two important results: 1) strongly significant host-specific sequence variation within the endolysin, and 2) a protein domain architecture apparently unique to our phage genomes in which the endolysin is located upstream of its associated holin. Endolysin sequences from our phages were one of two very distinct genotypes distinguished by variability within the putative enzymatically-active domain. The shared or core genome was comprised of genes with multiple sequence types belonging to five pfam families, and genes belonging to 12 pfam families, including the holin genes, which were nearly identical.ConclusionsSignificant genomic diversity exists even among closely-related bacteriophages. Holins and endolysins represent conserved functions across divergent phage genomes and, as we demonstrate here, endolysins can have significant variability and host-specificity even among closely-related genomes. Endolysins in our phage genomes may be subject to different selective pressures than the rest of the genome. These findings may have important implications for potential biotechnological applications of phage gene products.
Highlights
Because biotechnological uses of bacteriophage gene products as alternatives to conventional antibiotics will require a thorough understanding of their genomic context, we sequenced and analyzed the genomes of four closely related phages isolated from Clostridium perfringens, an important agricultural and human pathogen
C. perfringens is considered the cause of necrotic enteritis among chickens, and this does not generally present a threat to humans, it could potentially become a far greater problem for the poultry industry and consumers if antibiotics are withdrawn from animal feeds [13,14]
All four genomes were similar to the genome of FCP39O, previously published by our research group [6], and belonged to a larger clade (Figure 1B, 1C) containing FCPV1, a C. perfringens phage isolated in Russia [7]
Summary
Because biotechnological uses of bacteriophage gene products as alternatives to conventional antibiotics will require a thorough understanding of their genomic context, we sequenced and analyzed the genomes of four closely related phages isolated from Clostridium perfringens, an important agricultural and human pathogen. Since its enactment in 2006, the EU-wide ban on the use of antibiotics in animal feed (Regulation 1831/2003/ EC) has stimulated a renewed interest in bacteriophage. Clostridium perfringens bacteriophages [6,7] and demonstrated efficacy of the lytic proteins encoded by the bacteriophage endolysins as a C. perfringens antimicrobial [8]. These phages belonged to the Siphoviridae, a family within the tailed phages. C. perfringens is considered the cause of necrotic enteritis among chickens, and this does not generally present a threat to humans, it could potentially become a far greater problem for the poultry industry and consumers if antibiotics are withdrawn from animal feeds [13,14]
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