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PLoS Pathog. 2015 Oct 27;11(10):e1005244. doi: 10.1371/journal.ppat.1005244. eCollection 2015 Oct.

Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins.

Author information

1
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan; Institute for Advanced Study, Kyushu University, Fukuoka, Japan.
2
Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.
3
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.

Abstract

Transglutaminase (TG) catalyzes protein-protein crosslinking, which has important and diverse roles in vertebrates and invertebrates. Here we demonstrate that Drosophila TG crosslinks drosocrystallin, a peritrophic matrix protein, to form a stable fiber structure on the gut peritrophic matrix. RNA interference (RNAi) of the TG gene was highly lethal in flies and induced apoptosis of gut epithelial cells after oral infection with Pseudomonas entomophila. Moreover, AprA, a metalloprotease secreted by P. entomophila, digested non-crosslinked drosocrystallin fibers, but not drosocrystallin fibers crosslinked by TG. In vitro experiments using recombinant drosocrystallin and monalysin proteins demonstrated that monalysin, a pore-forming exotoxin of P. entomophila, was adsorbed on the crosslinked drosocrystallin fibers in the presence of P. entomophila culture supernatant. In addition, gut-specific TG-RNAi flies had a shorter lifespan than control flies after ingesting P. entomophila, whereas the lifespan after ingesting AprA-knockout P. entomophila was at control levels. We conclude that drosocrystallin fibers crosslinked by TG, but not non-crosslinked drosocrystallin fibers, form an important physical barrier against exotoxins of invading pathogenic microbes.

PMID:
26506243
PMCID:
PMC4646701
DOI:
10.1371/journal.ppat.1005244
[Indexed for MEDLINE]
Free PMC Article

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