A new article published in Frontiers in Cellular and Infection Microbiology discussed that 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. The authors described that 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 lead 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, the authors reported that hldE plays a major role for ETEC virulence. They demonstrated that the deletion of hldE resulted in markedly reduced binding to the human intestinal cells due to suppressed 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. Additionally, the hldE mutant displayed an altered growth, increased biofilm formation, and clumping in minimal growth medium. Furthermore, 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. Therefore, it was concluded that HldE is an attractive target for the development of future antimicrobial therapeutics.