Open AccessLipopolysaccharide O structure of adherent and invasive Escherichia coli regulates intestinal inflammation via complement C3
Author(s) -
Masashi Ohno,
Mizuho Hasegawa,
Akira Hayashi,
Gustavo Caballero-Flores,
Christopher J. Alteri,
Trevor D. Lawley,
Nobuhiko Kamada,
Gabriel Núñez,
Naohiro Inohara
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008928
Subject(s) - biology , microbiology and biotechnology , dysbiosis , lipopolysaccharide , escherichia coli , mutant , complement system , inflammation , bacteria , colitis , gene , immunology , immune system , genetics , gut flora
Gut dysbiosis associated with intestinal inflammation is characterized by the blooming of particular bacteria such as adherent-invasive E . coli (AIEC). However, the precise mechanisms by which AIEC impact on colitis remain largely unknown. Here we show that antibiotic-induced dysbiosis worsened chemically-induced colitis in IL-22-deficient mice, but not in wild-type mice. The increase in intestinal inflammation was associated with the expansion of E . coli strains with genetic and functional features of AIEC. These E . coli isolates exhibited high ability to out compete related bacteria via colicins and resistance to the host complement system in vitro . Mutation of wzy , the lipopolysaccharide O polymerase gene, rendered AIEC more sensitive to the complement system and more susceptible to engulfment and killing by phagocytes while retaining its ability to outcompete related bacteria in vitro. The wzy AIEC mutant showed impaired fitness to colonize the intestine under colitic conditions, but protected mice from chemically-induced colitis. Importantly, the ability of the wzy mutant to protect from colitis was blocked by depletion of complement C3 which was associated with impaired intestinal eradication of AIEC in colitic mice. These studies link surface lipopolysaccharide O-antigen structure to the regulation of colitic activity in commensal AIEC via interactions with the complement system.