Abstract
The Haemophilus influenzae HMW1 adhesin is a high-molecular weight protein that is secreted by the bacterial two-partner secretion pathway and mediates adherence to respiratory epithelium, an essential early step in the pathogenesis of H. influenzae disease. In recent work, we discovered that HMW1 is a glycoprotein and undergoes N-linked glycosylation at multiple asparagine residues with simple hexose units rather than N-acetylated hexose units, revealing an unusual N-glycosidic linkage and suggesting a new glycosyltransferase activity. Glycosylation protects HMW1 against premature degradation during the process of secretion and facilitates HMW1 tethering to the bacterial surface, a prerequisite for HMW1-mediated adherence. In the current study, we establish that the enzyme responsible for glycosylation of HMW1 is a protein called HMW1C, which is encoded by the hmw1 gene cluster and shares homology with a group of bacterial proteins that are generally associated with two-partner secretion systems. In addition, we demonstrate that HMW1C is capable of transferring glucose and galactose to HMW1 and is also able to generate hexose-hexose bonds. Our results define a new family of bacterial glycosyltransferases.
Highlights
Glycosylation of proteins is an essential process that plays an important role in protein structure and function and represents a strategy to fine tune cell-cell recognition and signaling
Haemophilus influenzae is a common cause of both bacterial respiratory tract disease and bacterial invasive disease and initiates infection by colonizing the upper respiratory tract
The Haemophilus HMW1 adhesin is a large protein that resides on the bacterial surface and mediates bacterial attachment to respiratory epithelial cells, an essential step in the process of colonization
Summary
Glycosylation of proteins is an essential process that plays an important role in protein structure and function and represents a strategy to fine tune cell-cell recognition and signaling. For a long period of time, glycosylation of proteins was believed to be restricted to eukaryotes. Nonencapsulated (nontypable) Haemophilus influenzae is a human specific pathogen that is a common cause of localized respiratory tract and invasive disease and initiates infection by colonizing the upper respiratory tract [11,12]. 75–80% of isolates express two related high-molecular weight proteins called HMW1 and HMW2 that mediate high-level adherence to respiratory epithelial cells and facilitate the process of colonization [13,14]. The HMW1 and HMW2 adhesins are encoded by homologous chromosomal loci that appear to represent a gene duplication event and contain 3 genes, designated hmw1A, hmw1B, and hmw1C and hmw2A, hmw2B, and hmw2C, respectively [15,16]
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