TY - JOUR
T1 - Bacteroides fragilis toxin expression enables lamina propria niche acquisition in the developing mouse gut
AU - Hill, Craig A.
AU - Casterline, Benjamin W.
AU - Valguarnera, Ezequiel
AU - Hecht, Aaron L.
AU - Shepherd, Elizabeth Stanley
AU - Sonnenburg, Justin L.
AU - Bubeck Wardenburg, Juliane
N1 - Publisher Copyright:
© 2024, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2024/1
Y1 - 2024/1
N2 - Bacterial toxins are well-studied virulence factors; however, recent studies have revealed their importance in bacterial niche adaptation. Enterotoxigenic Bacteroides fragilis (ETBF) expresses B. fragilis toxin (BFT) that we hypothesized may contribute to both colonic epithelial injury and niche acquisition. We developed a vertical transmission model for ETBF in mice that showed that BFT enabled ETBF to access a lamina propria (LP) niche during colonic microbiome development that was inaccessible to non-toxigenic B. fragilis. LP entry by ETBF required BFT metalloprotease activity, and showed temporal restriction to the pre-weaning period, dependent on goblet-cell-associated passages. In situ single-cell analysis showed bft expression at the apical epithelial surface and within the LP. BFT expression increased goblet cell number and goblet-cell-associated passage formation. These findings define a paradigm by which bacterial toxin expression specifies developmental niche acquisition, suggesting that a selective advantage conferred by a toxin may impact long-term host health.
AB - Bacterial toxins are well-studied virulence factors; however, recent studies have revealed their importance in bacterial niche adaptation. Enterotoxigenic Bacteroides fragilis (ETBF) expresses B. fragilis toxin (BFT) that we hypothesized may contribute to both colonic epithelial injury and niche acquisition. We developed a vertical transmission model for ETBF in mice that showed that BFT enabled ETBF to access a lamina propria (LP) niche during colonic microbiome development that was inaccessible to non-toxigenic B. fragilis. LP entry by ETBF required BFT metalloprotease activity, and showed temporal restriction to the pre-weaning period, dependent on goblet-cell-associated passages. In situ single-cell analysis showed bft expression at the apical epithelial surface and within the LP. BFT expression increased goblet cell number and goblet-cell-associated passage formation. These findings define a paradigm by which bacterial toxin expression specifies developmental niche acquisition, suggesting that a selective advantage conferred by a toxin may impact long-term host health.
UR - http://www.scopus.com/inward/record.url?scp=85181213105&partnerID=8YFLogxK
U2 - 10.1038/s41564-023-01559-9
DO - 10.1038/s41564-023-01559-9
M3 - Article
C2 - 38168616
AN - SCOPUS:85181213105
SN - 2058-5276
VL - 9
SP - 85
EP - 94
JO - Nature microbiology
JF - Nature microbiology
IS - 1
ER -