The Promise and Pitfalls of Prophages

Abstract

Phages dominate every ecosystem on the planet. While virulent phages sculpt the microbiome by killing their bacterial hosts, temperate phages provide unique growth advantages to their hosts through lysogenic conversion. Many prophages benefit their host, and prophages are responsible for genotypic and phenotypic differences that separate individual microbial strains. However, the microbes also endure a cost to maintain those phages: additional DNA to replicate and proteins to transcribe and translate. We have never quantified those benefits and costs. Here, we analysed over two and a half million prophages from over half a million bacterial genome assemblies. Analysis of the whole dataset and a representative subset of taxonomically diverse bacterial genomes demonstrated that the normalised prophage density was uniform across all bacterial genomes above 2 Mbp. We identified a constant carrying capacity of phage DNA per bacterial DNA. We estimated that each prophage provides cellular services equivalent to approximately 2.4 % of the cell’s energy or 0.9 ATP per bp per hour. We demonstrate analytical, taxonomic, geographic, and temporal disparities in identifying prophages in bacterial genomes that provide novel targets for identifying new phages. We anticipate that the benefits bacteria accrue from the presence of prophages balance the energetics involved in supporting prophages. Furthermore, our data will provide a new framework for identifying phages in environmental datasets, diverse bacterial phyla, and from different locations.

Prophages: an integral but understudied component of the human microbiome

“…All 949 935 publicly accessible bacterial genomes (as of 1 June 2022) listed in the dataset ‘NCBI Genome Assemblies Summary Archive 20220601’ (key resources) were downloaded from GenBank for analysis on the Flinders University HPC cluster [27]. PhiSpy [28, 29] was used to predict all of the prophages in all the bacterial genome assemblies, and we identified more than 5 million high-quality prophages [1]. PhiSpy was used as it is currently among the most accurate prophage prediction tools with the lowest runtime [30].…”

“…We also removed genomes consisting of more than 50 contigs as low quality; this cutoff ensures an average fragment length greater than 60 kb (for a typical 3 Mb genome) which was the upper length limit for almost all prophages reported in McKerral et al . [ 1 ]. Duplicate genome sequences were removed using the NCBI Genome Assemblies Summary (Key Resources ‘NCBI Genome Assemblies Summary Archive 20220601’).…”

“…The datasets created/analysed in this study are available at: NCBI Genome Assemblies Summary Archive 20220601 [1, 2], https://doi.org/10.25451/flinders.22299664.v2; Prophage predictions [1, 3], https://doi.org/10.25451/flinders.c.6629843 ; Archive of the PATRIC Metadata from 20220601 [1, 4], https://doi.org/10.25451/flinders.22299655.v2 ; Prophages in humans (this paper), https://doi.org/10.25451/flinders.24564379.v3…”

Meeting Report of the Second Symposium of the Belgian Society for Viruses of Microbes and Launch of the Phage Valley

“…The session started with the talk from Susanna Grigson (Flinders University, Adelaide, SA, Australia) about Phynteny: Synteny-based annotation of viral genes. Susanna pointed out that efficient annotation is fundamental to unraveling many aspects of viral processes [ 13 , 14 ]. Commonly used methods result in the assignment of the biological function to only 35% of the phage genes.…”

Growth and Genome Features of Non-O1/O139 Vibrio cholerae Isolated from Three Species of Common Freshwater Fish

“…Phages dominate the aquatic ecosystems on the Earth [32]. To the best of our knowledge, the current literature on prophages in V. cholerae genomes is rare.…”