Sialylation of lipooligosaccharides is dispensable for the virulence of haemophilus ducreyi in humans

Stanley Spinola, Wei Li, Kate R. Fortney, Diane Janowicz, Beth Zwickl, Barry Katz, Robert S. Munson

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Sialylated glycoconjugates on the surfaces of mammalian cells play important roles in intercellular communication and selfrecognition. 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.

Original languageEnglish
Pages (from-to)679-687
Number of pages9
JournalInfection and Immunity
Volume80
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Haemophilus ducreyi
Virulence
Sialyltransferases
Glycolipids
N-Acetylneuraminic Acid
Sialic Acid Binding Immunoglobulin-like Lectins
Chancroid
Molecular Mimicry
Glycoconjugates
Ligases
Phagocytosis
Innate Immunity
Dendritic Cells
lipid-linked oligosaccharides
Volunteers
Nucleotides
Macrophages
Tissue Donors
Phenotype
Infection

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Sialylation of lipooligosaccharides is dispensable for the virulence of haemophilus ducreyi in humans. / Spinola, Stanley; Li, Wei; Fortney, Kate R.; Janowicz, Diane; Zwickl, Beth; Katz, Barry; Munson, Robert S.

In: Infection and Immunity, Vol. 80, No. 2, 02.2012, p. 679-687.

Research output: Contribution to journalArticle

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