Biology subjects

Docherty, J. A. D.

Publications and source records attributed to Docherty, J. A. D..

3 recordsLinked to original sources

bioRxiv2026

Defining the ESKAPE pathogen prophage repertoire with PHORAGER

Prophages are major drivers of bacterial evolution, mediating horizontal gene transfer and lysogenic conversion to alter host phenotypes. Nevertheless, identifying prophages within bacterial genomes remains challenging due to their heterogeneity and similarity to other mobile genetic elements. Here we present PHORAGER (Prophage Hunting, vOtu Retrieval, Annotation and Genomic ExploRation), a scalable Nextflow pipeline for the standardised identification and quality assessment of prophages from bacterial genomes. PHORAGER incorporates bacterial genome pre-processing, consolidation of predictions from multiple mining tools, annotation-based filtering to reduce false positives, and generation of ready-to-analyse summary tables. We validated PHORAGER using 30,824 publicly available ESKAPE pathogen genomes. PHORAGER recovered more high-quality prophages than individual mining tools alone, and through extensive quality assessments removed a substantial number of false-positive predictions. In total 23,132 putative prophages were identified, the majority belonging to the class Caudoviricetes, and exhibiting a high degree of host-specificity. Putative antimicrobial resistance genes were detected in 0.48% of prophages, whereas virulence factors were most abundant in S. aureus prophages. ESKAPE prophages also frequently encoded anti-phage defence systems. PHORAGER is freely available as open-source software and the ESKAPE prophage collection generated in this study provides a reusable resource for further investigations. GRAPHICAL ABTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/742953v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1ce582org.highwire.dtl.DTLVardef@11fc004org.highwire.dtl.DTLVardef@17765f5org.highwire.dtl.DTLVardef@1c6f0ff_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2026

Comprehensive profiling of infant gut virome assembly reveals associations with eczema and wheeze

Infancy is a critical developmental window during which the gut ecosystem assembles and helps train the immune system, thereby setting trajectories for lifelong health. Bacteria and viruses are equally numerous in this early ecosystem, yet the gut viromes composition, dynamics, and health relevance remain poorly understood. Here, we show that the infant gut virome is diverse, dynamic, and linked to health outcomes. We performed comprehensive virome profiling of 1,110 longitudinal fecal samples from 314 mother-infant pairs from the Dutch birth cohort Lifelines NEXT using both virus-like particle enrichment (VLP) and total metagenomic sequencing (MGS). We find only 18.9% compositional overlap between the VLP- and MGS-metaviromes, with VLP recovering the active virome and most novel species and MGS predominantly capturing temperate phages. By combining both methods, we identified 8,348 novel virus species spanning diverse hosts, from bacteria to humans, and all major viral genome types (dsDNA, ssDNA, and RNA). We find that bacteriophages frequently encode metabolic functions, including genes related to B vitamin metabolism. We further observe that the development of the infant gut virome is shaped by both host factors, including delivery mode and feeding practices, and continuous switching of temperate phage lifecycles. Notably, the relative abundance of induced temperate phages is also associated with eczema development within the first year of life. Together, these findings establish the infant gut virome as a dynamic and clinically relevant component of early-life microbial development and highlight how comprehensive dual-method profiling is a necessary framework for future virome research.

microbiology↗

bioRxiv2026

Prophages of infant-derived Bifidobacterium longum subspecies employ antagonistic and synergistic strategies to persist in their host

Early colonisation by bifidobacteria is crucial for infant health, with Bifidobacterium longum subspecies (BL.) dominating the early gut microbiome. However, the interactions between these bacteria and their viruses remain poorly characterised. Here, we applied genomics-based approaches to examine BL. prophage composition and dynamics in infants, as well as their antagonistic and mutualistic evolutionary strategies. Across 213 metagenome-assembled genomes recovered from 139 infant faecal samples in the Dutch Lifelines NEXT cohort, 286 previously undescribed prophages were identified and analysed. Comparative genomics revealed extensive viral diversity, evidence of historical recombination, and widespread counter-defence, with [~]80% of prophages encoding anti-CRISPR or CRISPR-evasion proteins. Approximately half of prophages encoded metabolism altering genes. Notably, prophages and host CRISPR spacer arrays were highly stable across longitudinal samples, indicating stable phage-host associations during early life. Together, these findings show that BL. prophages employ antagonistic and synergistic strategies to maintain infectivity and long-term persistence in the infant gut.

microbiology↗