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Image_1_HldE Is Important for Virulence Phenotypes in Enterotoxigenic Escherichia coli.TIF

By Grith M. Maigaard Hermansen (5600555), Anders Boysen (627721), Thøger J. Krogh (5600558), Arkadiusz Nawrocki (344466), Lars Jelsbak (454810) and Jakob Møller-Jensen (231833)

Abstract

<p>Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrheal illness in third world countries and it especially affects children and travelers visiting these regions. ETEC causes disease by adhering tightly to the epithelial cells in a concerted effort by adhesins, flagella, and other virulence-factors. When attached ETEC secretes toxins targeting the small intestine host-cells, which ultimately leads to osmotic diarrhea. HldE is a bifunctional protein that catalyzes the nucleotide-activated heptose precursors used in the biosynthesis of lipopolysaccharide (LPS) and in post-translational protein glycosylation. Both mechanisms have been linked to ETEC virulence: Lipopolysaccharide (LPS) is a major component of the bacterial outer membrane and is needed for transport of heat-labile toxins to the host cells, and ETEC glycoproteins have been shown to play an important role for bacterial adhesion to host epithelia. Here, we report that HldE plays an important role for ETEC virulence. Deletion of hldE resulted in markedly reduced binding to the human intestinal cells due to reduced expression of colonization factor CFA/I on the bacterial surface. Deletion of hldE also affected ETEC motility in a flagella-dependent fashion. Expression of both colonization factors and flagella was inhibited at the level of transcription. In addition, the hldE mutant displayed altered growth, increased biofilm formation and clumping in minimal growth medium. Investigation of an orthogonal LPS-deficient mutant combined with mass spectrometric analysis of protein glycosylation indicated that HldE exerts its role on ETEC virulence both through protein glycosylation and correct LPS configuration. These results place HldE as an attractive target for the development of future antimicrobial therapeutics.</p

Topics: Clinical Microbiology, Medical Bacteriology, Medical Infection Agents (incl. Prions), Medical Virology, enterotoxigenic Escherichia coli, Lipopolysaccharide, ADP-l-glycero-β-d-manno-heptose, HldE, biofilm formation, motility, transmission electron microscopy, virulence factors
Year: 2018
DOI identifier: 10.3389/fcimb.2018.00253.s001
OAI identifier: oai:figshare.com:article/6940151
Provided by: FigShare
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