Sialylation of Lipooligosaccharides Is Dispensable for the Virulence of Haemophilus ducreyi in Humans
| Autor: | Wei Li, Stanley M. Spinola, Beth W. Zwickl, Barry P. Katz, Diane M. Janowicz, Kate R. Fortney, Robert S. Munson |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Lipopolysaccharides Male Sialyltransferase Immunology Mutant Virulence medicine.disease_cause Microbiology Chancroid Haemophilus ducreyi chemistry.chemical_compound Young Adult Bacterial Proteins Phagocytosis medicine Humans Innate immune system biology Macrophages Dendritic Cells Gene Expression Regulation Bacterial Middle Aged biology.organism_classification Molecular Pathogenesis N-Acetylneuraminic Acid Sialic acid Molecular mimicry Infectious Diseases chemistry Mutation biology.protein Parasitology Female N-Acetylneuraminic acid |
| Popis: | Sialylated glycoconjugates on the surfaces of mammalian cells play important roles in intercellular communication and self-recognition. The sialic acid preferentially expressed in human tissues is N -acetylneuraminic acid (Neu5Ac). In a process called molecular mimicry, many bacterial pathogens decorate their cell surface glycolipids with Neu5Ac. Incorporation of Neu5Ac into bacterial glycolipids promotes bacterial interactions with host cell receptors called Siglecs. These interactions affect bacterial adherence, resistance to serum killing and phagocytosis, and innate immune responses. Haemophilus ducreyi , the etiologic agent of chancroid, expresses lipooligosaccharides (LOS) that are highly sialylated. However, an H. ducreyi sialyltransferase ( lst ) mutant, whose LOS contain reduced levels of Neu5Ac, is fully virulent in human volunteers. Recently, a second sialyltransferase gene ( Hd0053 ) was discovered in H. ducreyi , raising the possibility that Hd0053 compensated for the loss of lst during human infection. CMP-Neu5Ac is the obligate nucleotide sugar donor for all bacterial sialyltransferases; LOS derived from an H. ducreyi CMP-Neu5Ac synthetase ( neuA ) mutant has no detectable Neu5Ac. Here, we compared an H. ducreyi neuA mutant to its wild-type parent in several models of pathogenesis. In human inoculation experiments, the neuA mutant formed papules and pustules at rates that were no different than those of its parent. When grown in media with and without Neu5Ac supplementation, the neuA mutant and its parent had similar phenotypes in bactericidal, macrophage uptake, and dendritic cell activation assays. Although we cannot preclude a contribution of LOS sialylation to ulcerative disease, these data strongly suggest that sialylation of LOS is dispensable for H. ducreyi pathogenesis in humans. |
| Databáze: | OpenAIRE |
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