Abstract
Bacteriophage associated with the human gut microbiome are likely to have an important impact on community structure and function, and provide a wealth of biotechnological opportunities. Despite this, knowledge of the ecology and composition of bacteriophage in the gut bacterial community remains poor, with few well characterized gut-associated phage genomes currently available. Here we describe the identification and in-depth (meta)genomic, proteomic, and ecological analysis of a human gut-specific bacteriophage (designated φB124-14). In doing so we illuminate a fraction of the biological dark matter extant in this ecosystem and its surrounding eco-genomic landscape, identifying a novel and uncharted bacteriophage gene-space in this community. φB124-14 infects only a subset of closely related gut-associated Bacteroides fragilis strains, and the circular genome encodes functions previously found to be rare in viral genomes and human gut viral metagenome sequences, including those which potentially confer advantages upon phage and/or host bacteria. Comparative genomic analyses revealed φB124-14 is most closely related to φB40-8, the only other publically available Bacteroides sp. phage genome, whilst comparative metagenomic analysis of both phage failed to identify any homologous sequences in 136 non-human gut metagenomic datasets searched, supporting the human gut-specific nature of this phage. Moreover, a potential geographic variation in the carriage of these and related phage was revealed by analysis of their distribution and prevalence within 151 human gut microbiomes and viromes from Europe, America and Japan. Finally, ecological profiling of φB124-14 and φB40-8, using both gene-centric alignment-driven phylogenetic analyses, as well as alignment-free gene-independent approaches was undertaken. This not only verified the human gut-specific nature of both phage, but also indicated that these phage populate a distinct and unexplored ecological landscape within the human gut microbiome.
Highlights
The human gut harbours a diverse microbial community which in turn plays host to a variety of mobile genetic elements (MGE) and bacteriophages, forming the gut mobile metagenome [1,2,3,4]
Using comparative metagenomic analysis and genome signature-based approaches we subsequently examined its ecological profile in relation to 611 other bacteriophage genomes available on GenBank, as well as human gut-specific viral metagenomes [6]
Results and Discussion wB124-14 physical characteristics and host range Transmission Electron Microscopy (TEM) shows wB124-14 has a binary morphology with an icosahedral head and a noncontractile tail (Figure 1A), placing it in the Caudoviriale order, Siphoviridae family [30]
Summary
The human gut harbours a diverse microbial community which in turn plays host to a variety of mobile genetic elements (MGE) and bacteriophages, forming the gut mobile metagenome [1,2,3,4]. Based on sequence homology and conserved domain searches, the wB124-14 ORF8 appears to encode a ThyA type enzyme which is predicted to be utilised by ,70% of microorganisms [46], but seemingly rare in human gut viral genomes and most likely acquired from host bacterial species [6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
