---
title: "ARG-PASS v2.0 reveals previously unrecognized **antibiotic resistance genes** reaching the human g"
id: "biorxiv-15-arg-pass-v2-0-expands-global-resistome-surveillance-to-reveal-previously"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-15-arg-pass-v2-0-expands-global-resistome-surveillance-to-reveal-previously"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.21.760772v1?rss=1"
published_at: "2026-10-22T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# ARG-PASS v2.0 reveals previously unrecognized **antibiotic resistance genes** reaching the human g
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-15-arg-pass-v2-0-expands-global-resistome-surveillance-to-reveal-previously
- **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/10.64898/2026.10.21.760772v1?rss=1)
- **Published At:** 2026-10-22T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study introduces **ARG-PASS v2.0** (ARG-prediction by PAirwise Sequence versus Structure v2.0), a computational pipeline designed to detect divergent antibiotic resistance genes (ARGs) that share limited sequence similarity with characterised enzymes. - Investigators applied the tool to a lake metagenome from Kolkata, India; of 11 candidate ARGs selected for experimental testing, the team reported functional confirmation in Escherichia coli for 10 candidates across multiple ARG classes. - The authors predicted 918 **class B1 metallo-beta-lactamases (MBLs)** from public sequence repositories (MGnify and PLSDB), most of which diverged from characterised enzymes but appeared widely distributed across environments. - Phylogenetic analysis placed clinically relevant class B1 MBLs within diversity sampled from marine sources, and the authors suggested a possible marine reservoir. - Cross-referencing against the Unified Human Gastrointestinal Protein catalogue recovered a carbapenemase, an ANT (aminoglycoside nucleotidyltransferase), and class A beta-lactamases from Bacillus sonorensis and Bacillus licheniformis. - Those Bacillus-derived ARGs were detected in South Korean fermented soybean paste (doenjang) and in gut isolates from populations consuming those foods, consistent with a food-associated route into the human microbiome. - The dataset and analyses point to a largely chromosomal reservoir of previously undescribed ARG diversity that can reach the human gut via resident and generalist hosts. - Authors note that the environmental resistome remains poorly described and that surveillance to date has largely targeted ARGs resembling already clinically characterised genes; routes from environment to human pathogens remain an unresolved research question. - This work is reported as a preprint and has not been peer reviewed; the source did not report clinical impact metrics, detailed experimental protocols for all validations, or specific timelines for regulatory follow-up.
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Lachlan Bartrop 1 Université de Sherbrooke; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Lachlan%2BBartrop%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bartrop%20L&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ALachlan%2BBartrop%2B) Frédéric Grenier 1 Université de Sherbrooke; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Fr%C3%A9d%C3%A9ric%2BGrenier%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Grenier%20F&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AFr%25C3%25A9d%25C3%25A9ric%2BGrenier%2B) Joseph Bielawski 2 Dalhousie University * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Joseph%2BBielawski%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bielawski%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJoseph%2BBielawski%2B) Sébastien Rodrigue 1 Université de Sherbrooke; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=S%C3%A9bastien%2BRodrigue%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Rodrigue%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AS%25C3%25A9bastien%2BRodrigue%2B) Louis-Patrick Haraoui 1 Université de Sherbrooke; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Louis-Patrick%2BHaraoui%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Haraoui%20L&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ALouis-Patrick%2BHaraoui%2B) * [ORCID record for Louis-Patrick Haraoui](http://orcid.org/0000-0002-3713-7866 "Open in new tab") * For correspondence: louis.patrick.haraoui@usherbrooke.ca * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.21.760772v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5894329/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.21.760772v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5894329/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.21.760772v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5894329/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.21.760772v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5894329/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.21.760772v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5894329/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Antimicrobial resistance (AMR) is a significant global public health threat, and antibiotic resistance genes (ARGs) that bacteria depend on to withstand treatment are its molecular basis. How ARGs move from environmental reservoirs into the human microbiome, and eventually into human pathogens, remains one of the most important unresolved questions in AMR research. Surveillance has largely targeted ARGs resembling those already clinically characterised. The environmental reservoir remains poorly described and the routes connecting it to human microbiomes are inferred rather than observed. Describing that reservoir requires computational methods able to recognise ARGs that share little similarity with known enzymes, yet retain accuracy after experimental validation to enable scalable applications. Dietary exposure through unprocessed ferments offers a tractable setting in which such a route can be observed directly. Here we introduce ARG-PASS v2.0 (ARG-prediction by PAirwise Sequence versus Structure v2.0) and first apply it to a lake metagenome from Kolkata, India, where 10 of 11 tested candidates across diverse ARG classes were functionally confirmed after expression in Escherichia coli. Given their clinical relevance, we then predicted 918 class B1 metallo-beta-lactamases (MBLs) from MGnify and the PLSDB, with most diverging from characterised enzymes, but as widely distributed. A number of globally widespread candidates track their hosts distribution, with some recovered only from human-associated biomes, yet most span a wider ecological range. Phylogenetic inference places clinically relevant class B1 MBLs within marine diversity and suggests a marine reservoir. Cross-referencing against the Unified Human Gastrointestinal Protein catalogue identified a carbapenemase, an ANT, and class A beta-lactamases from Bacillus sonorensis and Bacillus licheniformis, detected in South Korean fermented soybean paste (doenjang) as well as gut isolates of populations consuming these foods. Together, these results point to a largely chromosomal reservoir of undescribed ARG diversity that reaches the human gut through both resident and generalist hosts. Once in the human microbiome, treatment may be compromised directly if the host is an opportunistic pathogen, or after transfer to a clinical pathogen. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared CIFAR's Humans & the Microbiome Research Program Génome Québec, https://ror.org/00xhtr962 Fonds de Recherche du Québec - Santé, https://ror.org/02eqrsj93, 349522 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/10.64898/2026.10.21.760772v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/22/2026.10.21.760772.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/10.64898/2026.10.21.760772v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) ARG-PASS v2.0 expands global resistome surveillance to reveal previously unrecognized antibiotic resistance genes reaching the human gut Lachlan Bartrop, Frédéric Grenier, Joseph Bielawski, Sébastien Rodrigue, Louis-Patrick Haraoui bioRxiv 2026.10.21.760772; doi: https://doi.org/10.64898/2026.10.21.760772 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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