---
title: "Huge phages carry diverse cell-envelope proteins including sortase B, PspA and β-barrel OMPs"
id: "biorxiv-2-large-genome-phages-encode-diverse-proteins-associated-with-host-cell-envelope"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-2-large-genome-phages-encode-diverse-proteins-associated-with-host-cell-envelope"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1?rss=1"
published_at: "2026-10-24T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Huge phages carry diverse cell-envelope proteins including sortase B, PspA and β-barrel OMPs
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-2-large-genome-phages-encode-diverse-proteins-associated-with-host-cell-envelope
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1?rss=1)
- **Published At:** 2026-10-24T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators analyzed protein families across 7,187 non-redundant genomes of **huge phages** (defined in the source as >200 kilobases). - Protein structure–based analyses revealed strong phylogenetic and habitat-associated diversification among dominant protein families in these genomes. - The study team identified phage-encoded proteins linked to bacterial cell envelope functions, with a concentration of such proteins in **human gut**-associated huge phages. - Authors reported previously unreported phage-encoded **sortase B**; predicted substrates contain signal peptides and cell-wall sorting signals, implying a route for surface display of phage proteins on bacterial hosts. - The cohort showed widespread occurrence of phage-encoded **phage shock protein A (PspA)** across diverse lineages; PspA genes frequently neighbored membrane organization and transport genes, suggesting membrane physiology roles. - Data indicated 1,603 β-barrel **outer membrane proteins (OMPs)** across 1,303 huge phages from varied ecosystems; these OMPs exhibited structural diversity linked to predicted host taxonomy, habitat, and neighboring envelope-related genes. - Metatranscriptomic analyses supported expression of representative phage-encoded **PspA** and **OMP** genes in natural communities, including the human gut. - Authors concluded that bacterial cell envelope processes represent an underappreciated interface for huge phage-host interactions. The source did not report experimental assays validating biochemical function of these phage-encoded proteins.
## Clinical Analysis & Structured Key Points
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LinXing Chen University of Science and Technology of China * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=LinXing%2BChen%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Chen%20L&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ALinXing%2BChen%2B) * [ORCID record for LinXing Chen](http://orcid.org/0000-0003-2774-1952 "Open in new tab") * For correspondence: linkingchan@gmail.com Ling Yuan University of Science and Technology of China * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ling%2BYuan%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Yuan%20L&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ALing%2BYuan%2B) * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5901251/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5901251/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5901251/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5901251/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5901251/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## 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 β-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. ### Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC 4.0 International license](http://creativecommons.org/licenses/by-nc/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/24/2026.10.24.761521.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.10.24.761521v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Large-genome phages encode diverse proteins associated with host cell envelope functions LinXing Chen, Ling Yuan bioRxiv 2026.10.24.761521; doi: https://doi.org/10.64898/2026.10.24.761521 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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