A microbiota-derived protease links phage susceptibility to host epithelial responses
- 1Host-Microbe Interactomics Lab, Institute of Medical Microbiology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
Abstract
Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.
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BibTeX
@misc{qu2026microbiotaderived,
title = {{A microbiota-derived protease links phage susceptibility to host epithelial responses}},
author = {N. Qu and M. S. Birk and T. C. A. Hitch and C. D. Rudder and B. Monteiro and M. K. Bandu and M. Gaissmaier and L. Michel and M. S. Matchado and C. G. P. Voogdt and A. Kriaa and N. S. Treichel and B. O. Schroeder and E. M. Buhl and C. Preisinger and A. Typas and B. Stecher and P. Wilmes and T. Clavel and J. Selkrig},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.26.754296},
url = {https://www.biorxiv.org/content/10.64898/2026.09.26.754296v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A microbiota-derived protease links phage susceptibility to host epithelial responses
AU - N. Qu
AU - M. S. Birk
AU - T. C. A. Hitch
AU - C. D. Rudder
AU - B. Monteiro
AU - M. K. Bandu
AU - M. Gaissmaier
AU - L. Michel
AU - M. S. Matchado
AU - C. G. P. Voogdt
AU - A. Kriaa
AU - N. S. Treichel
AU - B. O. Schroeder
AU - E. M. Buhl
AU - C. Preisinger
AU - A. Typas
AU - B. Stecher
AU - P. Wilmes
AU - T. Clavel
AU - J. Selkrig
PY - 2026
DA - 2026/09/26
PB - bioRxiv
DO - 10.64898/2026.09.26.754296
UR - https://www.biorxiv.org/content/10.64898/2026.09.26.754296v1
AB - Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.
ER -