Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome

Abstract

The mammalian gut ecosystem has significant influence on host physiology1–4, but the mechanisms that sustain this complex environment in the face of different stresses remain obscure. Perturbations to this ecosystem, such as through antibiotic treatment or diet, are currently interpreted at the level of bacterial phylogeny5–7. Less is known about the contributions of the abundant population of phage to this ecological network. Here, we explore the phageome as a potential genetic reservoir for bacterial adaptation by sequencing murine fecal phage populations following antibiotic perturbation. We show that antibiotic treatment leads to the enrichment of phage-encoded genes that confer resistance via disparate mechanisms to the administered drug as well as genes that confer resistance to antibiotics unrelated to the administered drug, and we demonstrate experimentally that phage from treated mice afford aerobically cultured naïve microbiota increased resistance. Systems-wide analyses uncover post-treatment phage-encoded processes related to host colonization and growth adaptation, indicating that the phageome broadly enriches for functionally beneficial genes under stress-related conditions. We also show that antibiotic treatment expands the interactions between phage and bacterial species, leading to a more highly connected phage-bacterial network for gene exchange. Our work implicates the phageome in the emergence of multidrug resistance and indicates that the adaptive capacity of the phageome may represent a community-based mechanism for protecting the gut microflora, preserving its functional robustness during antibiotic stress.

Depth-stratified functional and taxonomic niche specialization in the ‘core’ and ‘flexible’ Pacific Ocean Virome

“…Extensive BLAST-, kmer-and contig-based analyses of these viromes have suggested low bacterial contamination that compares quite favorably to others mined for AMG-like signals (o0.002% for POV ; vs o0.1% for the human phageome (Modi et al, 2013)). To more specifically investigate potential bacterial contamination in this study, we compared bacterial taxonomy associated with POV ORFs to 16S ribosomal RNA gene taxonomy in the PCE and ACE PCs, and found minimal parallels between these variables (Supplementary Figure S1).…”

Ecological and Evolutionary Benefits of Temperate Phage: What Does or Doesn't Kill You Makes You Stronger

“…[29] Temperate phages frequently encode antibiotic resistance genes and lysis induced by exposure to antibiotics has been shown to lead to mobilization of antibiotic resistance genes between bacterial hosts in the animal gut. [34] It is possible that the high proportion of prophages linked to pathogen associated traits represents a bias in the literature rather than a real biological phenomenon, indeed greater sequencing of environmental samples has revealed some surprising examples of phageencoded traits, including photosynthetic genes carried by a cyanophage. [35] 3…”

Synthetic biology devices for in vitro and in vivo diagnostics

“…These models gave rise to the notion that in vivo environmental cues could drive memory units, transforming bacterial host cells into diagnostic indicators for recording exposure events. One possible use could be the nondestructive interrogation of the human gut microbiome, which is intertwined with health, metabolism, and a growing list of disease states or conditions (49). To this end, E. coli were programmed to serve as "living diagnostics" and report environmental signals in the mouse gut (Fig.…”