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PreprintCC BY-NCbioRxiv

Large-genome phages encode diverse proteins associated with host cell envelope functions

  1. 1University of Science and Technology of China

Abstract

Huge phages (or jumbo phages, >200 kilobases) encode extensive protein repertoires, yet their functional diversity and potential roles in host physiology remain poorly understood. Using protein structure-based analyses of dominant protein families across 7,187 non-redundant genomes of huge phages, we uncovered pronounced phylogenetic and habitat-associated diversification. Notably, we identified diverse proteins associated with bacterial cell envelope functions, particularly in human gut-associated huge phages. These included previously unreported phage-encoded sortase B, whose putative substrates contain signal peptides and cell-wall sorting signals, suggesting a potential route for displaying phage proteins on bacterial surfaces. Phage-encoded phage shock protein A (PspA) was distributed across diverse lineages and frequently neighbored genes associated with membrane organization and transport, implicating potential roles in membrane physiology. We also identified 1,603 {beta}-barrel outer membrane proteins (OMPs) across 1,303 huge phages from diverse ecosystems. These OMPs exhibited structural diversity and associations with predicted host taxonomy, habitat, and neighboring envelope-related genes. Metatranscriptomic analysis supported expression of representative phage-encoded PspA and OMP genes in natural communities including the human gut. Together, these findings reveal bacterial cell envelope processes as a previously underappreciated potential interface for huge phage-host interactions.

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BibTeX
@misc{chen2026largegenome,
  title = {{Large-genome phages encode diverse proteins associated with host cell envelope functions}},
  author = {L. Chen and L. Yuan},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.24.761521},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - Large-genome phages encode diverse proteins associated with host cell envelope functions
AU  - L. Chen
AU  - L. Yuan
PY  - 2026
DA  - 2026/10/24
PB  - bioRxiv
DO  - 10.64898/2026.10.24.761521
UR  - https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1
AB  - Huge phages (or jumbo phages, >200 kilobases) encode extensive protein repertoires, yet their functional diversity and potential roles in host physiology remain poorly understood. Using protein structure-based analyses of dominant protein families across 7,187 non-redundant genomes of huge phages, we uncovered pronounced phylogenetic and habitat-associated diversification. Notably, we identified diverse proteins associated with bacterial cell envelope functions, particularly in human gut-associated huge phages. These included previously unreported phage-encoded sortase B, whose putative substrates contain signal peptides and cell-wall sorting signals, suggesting a potential route for displaying phage proteins on bacterial surfaces. Phage-encoded phage shock protein A (PspA) was distributed across diverse lineages and frequently neighbored genes associated with membrane organization and transport, implicating potential roles in membrane physiology. We also identified 1,603 {beta}-barrel outer membrane proteins (OMPs) across 1,303 huge phages from diverse ecosystems. These OMPs exhibited structural diversity and associations with predicted host taxonomy, habitat, and neighboring envelope-related genes. Metatranscriptomic analysis supported expression of representative phage-encoded PspA and OMP genes in natural communities including the human gut. Together, these findings reveal bacterial cell envelope processes as a previously underappreciated potential interface for huge phage-host interactions.
ER  -