Chancroid and Haemophilus ducreyi

Morse, Stephen

doi:10.1128/cmr.2.2.137

Cited by 211 publications

(179 citation statements)

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“…ducreyi has been shown to associate with human granulocytes and macrophages in chancroidal lesions that occur naturally (31,37) and in the human challenge model of infection (8,10,49). At least during the early stages of experimental infection (i.e., through pustule development), H. ducreyi can be found associated with PMNs and macrophages but not with T cells, Langerhans' cells, or fibroblasts (8).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Phagocytosis byHaemophilus ducreyiRequires Expression of the LspA1 and LspA2 Proteins

2003

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Haemophilus ducreyi previously has been shown to inhibit the phagocytosis of both secondary targets and itself by certain cells in vitro. Wild-type H. ducreyi strain 35000HP contains two genes, lspA1 and lspA2, whose encoded protein products are predicted to be 456 and 543 kDa, respectively. An isogenic mutant of H. ducreyi 35000HP with inactivated lspA1 and lspA2 genes has been shown to exhibit substantially decreased virulence in the temperature-dependent rabbit model for chancroid. This lspA1 lspA2 mutant was tested for its ability to inhibit phagocytosis of immunoglobulin G-opsonized particles by differentiated HL-60 and U-937 cells and by J774A.1 cells. The wild-type strain H. ducreyi 35000HP readily inhibited phagocytosis, whereas the lspA1 lspA2 mutant was unable to inhibit phagocytosis. Similarly, the wild-type strain was resistant to phagocytosis, whereas the lspA1 lspA2 mutant was readily engulfed by phagocytes. This inhibitory effect of wild-type H. ducreyi on phagocytic activity was primarily associated with live bacterial cells but could also be found, under certain conditions, in concentrated H. ducreyi culture supernatant fluids that lacked detectable outer membrane fragments. Both the wild-type strain and the lspA1 lspA2 mutant attached to phagocytes at similar levels. These results indicate that the LspA1 and LspA2 proteins of H. ducreyi are involved, directly or indirectly, in the antiphagocytic activity of this pathogen, and they provide a possible explanation for the greatly reduced virulence of the lspA1 lspA2 mutant.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Phagocytosis byHaemophilus ducreyiRequires Expression of the LspA1 and LspA2 Proteins

2003

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“…This fastidious microorganism is a strict human pathogen that localizes to the genital epithelia and does not cause systemic infection (39,65,75). Although H. ducreyi was first identified by Auguste Ducrey in 1889, the mechanisms responsible for the pathogenesis of chancroid remain poorly understood.…”

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confidence: 99%

A Novel Lectin, DltA, Is Required for Expression of a Full Serum Resistance Phenotype inHaemophilus ducreyi

Leduc¹,

Richards

Davis

et al. 2004

Infect Immun

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Haemophilus ducreyi, the causative agent of chancroid, is highly resistant to the complement-mediated bactericidal activity of normal human serum (NHS). Previously, we identified DsrA (for ducreyi serum resistance A), a major factor required for expression of the serum resistance phenotype in H. ducreyi. We describe here a second outer membrane protein, DltA (for ducreyi lectin A), which also contributes to serum resistance in H. ducreyi. Isogenic dltA mutants, constructed in 35000HP wild-type and FX517 dsrA backgrounds, were more susceptible to the bactericidal effects of NHS than each respective parent, demonstrating the additive effect of the mutations. Furthermore, expression of dltA in H. influenzae strain Rd rendered this highly susceptible strain partially resistant to 5% NHS compared to a vector-control strain. Although primary basic local alignment search tool analysis of the dltA open reading frame revealed no close bacterial homologue, similarity to the ␤-chain of the eukaryotic lectin ricin was noted. DltA shares highly conserved structural motifs with the ricin ␤ chain, such as cysteines and lectin-binding domains. To determine whether dltA was a lectin, ligand blots and affinity chromatography experiments were performed. DltA was affinity purified on immobilized lactose and N-acetylgalactosamine, and N-glycosylated but not glycosidase-treated model glycoproteins bound DltA. These data indicate that DltA is a lectin with specificity for lactose-related carbohydrates (CHO) and is important for H. ducreyi serum resistance.

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“…H. ducreyi is a strictly human pathogen that primarily infects the skin and mucous membranes. Little is known about the mechanisms by which H. ducreyi causes disease (31,46). H. ducreyi adheres to extracellular matrix proteins (1), several immortalized cell lines (27,28,37), human fibroblasts (3,28), and human keratinocytes in vitro (12,45).…”

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confidence: 99%

Fine tangled pili expressed by Haemophilus ducreyi are a novel class of pili

et al. 1996

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Haemophilus ducreyi synthesizes fine, tangled pili composed predominantly of a protein whose apparent molecular weight is 24,000 (24K). A hybridoma, 2D8, produced a monoclonal antibody (MAb) that bound to a 24K protein in H. ducreyi strains isolated from diverse geographic locations. A gt11 H. ducreyi library was screened with MAb 2D8. A 3.5-kb chromosomal insert from one reactive plaque was amplified and ligated into the pCRII vector. The recombinant plasmid, designated pHD24, expressed a 24K protein in Escherichia coli INV␣F that bound MAb 2D8. The coding sequence of the 24K gene was localized by exonuclease III digestion. The insert contained a 570-bp open reading frame, designated ftpA (fine, tangled pili). Translation of ftpA predicted a polypeptide with a molecular weight of 21.1K. The predicted N-terminal amino acid sequence of the polypeptide encoded by ftpA was identical to the N-terminal amino acid sequence of purified pilin and lacked a cleavable signal sequence. Primer extension analysis of ftpA confirmed the lack of a leader peptide. The predicted amino acid sequence lacked homology to known pilin sequences but shared homology with the sequences of E. coli Dps and Treponema pallidum antigen TpF1 or 4D, proteins which associate to form ordered rings. An isogenic pilin mutant, H. ducreyi 35000ftpA::mTn3(Cm), was constructed by shuttle mutagenesis and did not contain pili when examined by electron microscopy. We conclude that H. ducreyi synthesizes fine, tangled pili that are composed of a unique major subunit, which may be exported by a signal sequence independent mechanism.Haemophilus ducreyi is the causative agent of the genital ulcer disease chancroid (46). Genital ulcer disease due to H. ducreyi is an independent risk factor for human immunodeficiency virus seropositivity (24,44,46,47). H. ducreyi is a strictly human pathogen that primarily infects the skin and mucous membranes. Little is known about the mechanisms by which H. ducreyi causes disease (31, 46). H. ducreyi adheres to extracellular matrix proteins (1), several immortalized cell lines (27,28,37), human fibroblasts (3, 28), and human keratinocytes in vitro (12,45). However, the identities of the surface components that mediate adherence to human tissues and the cells to which H. ducreyi binds in vivo are presently unknown.Pili (fimbriae) are filamentous appendages present on the surface of most gram-negative bacteria and serve as adhesins. H. ducreyi synthesizes fine, tangled pili, the expression of which has been associated with binding to laminin (1, 40). Purified pili are composed predominantly of a major subunit whose apparent molecular weight is 24,000 (24K) as well as several minor higher-molecular-weight bands (18,22,40). Immunization with purified pili provides partial protection against experimental infection in the temperature-dependent rabbit model (18).In order to study the role of H. ducreyi pili in pathogenesis, we isolated a gene, designated ftpA (fine, tangled pili) that encodes the 24K protein. We show that FtpA lacked ...

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Chancroid and Haemophilus ducreyi

Cited by 211 publications

References 142 publications

Inhibition of Phagocytosis byHaemophilus ducreyiRequires Expression of the LspA1 and LspA2 Proteins

Inhibition of Phagocytosis byHaemophilus ducreyiRequires Expression of the LspA1 and LspA2 Proteins

A Novel Lectin, DltA, Is Required for Expression of a Full Serum Resistance Phenotype inHaemophilus ducreyi

Fine tangled pili expressed by Haemophilus ducreyi are a novel class of pili

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