Gut microbiome ADP-ribosyltransferases are widespread phage-encoded fitness factors

Bacteriophage-Mediated Perturbation of Defined Bacterial Communities in an In Vitro Model of the Human Gut

“…Before their use in perturbation experiments, a fraction of the PEG-purified D5 viruses were characterized by metagenomic sequencing. To complement these data, a fraction of D5 viruses was further purified on cesium chloride density gradients for transmission electron microscopy ( 6 ) imaging. Taxonomic assignment of contigs (see Materials and Methods) revealed a prevalence of phages belonging to the order Caudovirales (88.4%) and family Siphoviridae (77.3%) ( Fig.…”

“…Bacteriophages, or phages, are bacterial viruses. They are believed to influence human gut microbiomes by killing their bacterial hosts ( 1 , 4 ), encoding fitness factors that benefit bacterial hosts ( 5 , 6 ), and/or facilitating horizontal gene transfer ( 7 ). Because the bacterial portion of the gut microbiome is linked to a range of functions integral to host fitness ( 8 – 10 ), phage-bacteria dynamics are expected to have substantial impacts on human health.…”

“…They do not involve experimental control or manipulation. Over the last decade, these snapshots have revealed several interesting phenomena related to gastrointestinal phage communities, including enrichment with temperate phages ( 3 , 14 ), presence of gut-specialized phage taxa ( 15 ), and phage-encoded fitness factors that interact with mammal-encoded factors ( 5 , 6 ). If researchers are to begin understanding how these phenomena occur and why they have evolved in gastrointestinal ecosystems, platforms that enable experimental manipulation must be developed and trialed.…”

Phage Genome Diversity in a Biogas-Producing Microbiome Analyzed by Illumina and Nanopore GridION Sequencing

“…The activity of ADPRT was described to facilitate gaining control over the infected host cell primarily through shifting gene expression toward the phage genes at different stages of growth [66]. Brown and colleagues also assumed that many ADPRT-encoding genes are accessory genes that are horizontally transferred to confer a fitness advantage to the host [67,68]. Shmakov et al also predicted that ADPRT is usually encoded by CRISPR-Cas systems loci, which might help to stabilize the prophages and plasmids in the host bacteria [69].…”

Products of gut microbial Toll/interleukin-1 receptor domain NADase activities in gnotobiotic mice and Bangladeshi children with malnutrition

“…The mechanism involves bacterial nicotinamidase (PncA)-catalyzed conversion of nicotinamide to nicotinic acid, a deamidated precursor of NAD that is readily salvaged by the host through the Preiss-Handler pathway ( Preiss and Handler, 1958 ; Shats et al., 2020 ). Another example is provided by bacterially encoded ADP-ribosyltransferases (ADPRTs); a recent report ( Brown et al., 2021 ) indicated that bacteria express ADPRTs, which can utilize NAD to transfer ADP-ribose (ADPR) onto host proteins, stimulating release of inosine, a carbon source that is accessible to these bacteria. Furthermore, human gut microbial NAD metabolism has the capacity to modify pathologic processes, including certain forms of neurodegeneration (e.g., Blacher et al., 2019 ).…”