Most metagenomic vanT calls are not vancomycin resistance genes

Shetty, P.; Maroti, G.; Wirth, R.

doi:10.64898/2026.10.22.760690

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bioRxiv · 10.64898/2026.10.22.760690

Most metagenomic vanT calls are not vancomycin resistance genes

Shetty, P.·Maroti, G.·Wirth, R.

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Abstract

Metagenomic resistome surveys frequently report vanTG as the dominant glycopeptide resistance gene, but these calls rely on homology without verifying catalytic residues or operon context. By analyzing 107,008 metagenome-assembled genomes, we demonstrate that only 3.7% of predicted vanTG genes possess the required active-site substitution, with the vast majority being misannotated alanine racemases. Incorporating structural and genomic context corrections reveals a novel split-architecture lineage in gut-associated Erysipelotrichales missed by current profiling tools.

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Shetty, P., Maroti, G., Wirth, R.. 2026-10-23. Most metagenomic vanT calls are not vancomycin resistance genes. https://doi.org/10.64898/2026.10.22.760690

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