Haemophilus ducreyi, a cause of genital ulcer disease in developing countries, appears to facilitate the heterosexual transmission of the human immunodeficiency virus in Africa. Despite an increase in studies of this gram-negative human pathogen, little is known about the pathogenesis of chancroid. Our studies have shown that the lipooligosaccharides (LOS) of H. ducreyi may play an important role in ulcer formation. Monoclonal antibody and mass spectrometric analyses identified a terminal trisaccharide present on H. ducreyi LOS that is immunochemically similar to human paragloboside. This epitope is present on the LOS of Neisseria gonorrhoeae, and it may be the site of attachment for pyocin lysis. We have used pyocin, produced by Pseudomonas aeruginosa, to select LOS variants with sequential saccharide deletions from N. gonorrhoeae. On the basis of the similarities between N. gonorrhoeae and H. ducreyi LOS, we employed the same technique to determine if H. ducreyi strains were susceptible to pyocin lysis. In this study, we report the generation of a pyocin N-resistant H. ducreyi strain which synthesizes a truncated version of the parental LOS. Further studies have shown that this H. ducreyi variant has lost the terminal LOS epitope defined by monoclonal antibody 3F11. This report demonstrates that H. ducreyi is sensitive to pyocins and that this technique can be used to generate H. ducreyi LOS variants. Such variants could be used in comparative studies to relate LOS structure to biologic function in the pathogenesis of chancroid.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC186522PMC
http://dx.doi.org/10.1128/iai.62.6.2379-2386.1994DOI Listing

Publication Analysis

Top Keywords

ducreyi los
12
ducreyi
10
los
9
haemophilus ducreyi
8
ducreyi variant
8
pathogenesis chancroid
8
monoclonal antibody
8
pyocin lysis
8
los variants
8
pyocin
5

Similar Publications

Aetiological molecular identification of sexually transmitted infections that cause urethral discharge syndrome and genital ulcer disease in Brazilian men: a nationwide study.

Sex Transm Infect

April 2024

Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Secretariat of Health Surveillance, Ministry of Health, Brasília, Distrito Federal, Brazil.

Article Synopsis
  • Limited knowledge of urethral discharge syndrome (UDS) and genital ulcer disease (GUD) in Brazil prompted a nationwide study aimed at updating treatment guidelines from 2018 to 2020.
  • The study involved collecting samples from male participants across Brazil and utilized advanced PCR testing to identify various pathogens linked to UDS and GUD.
  • Findings revealed that Neisseria gonorrhoeae was the most common pathogen in UDS, while herpes simplex virus type 2 was most prevalent in GUD, highlighting significant coinfection rates and providing crucial insights into the local aetiology of these conditions.
View Article and Find Full Text PDF

Distinct Roles for CdtA and CdtC during Intoxication by Cytolethal Distending Toxins.

PLoS One

July 2016

Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America.

Cytolethal distending toxins (CDTs) are heterotrimeric protein exotoxins produced by a diverse array of Gram-negative pathogens. The enzymatic subunit, CdtB, possesses DNase and phosphatidylinositol 3-4-5 trisphosphate phosphatase activities that induce host cell cycle arrest, cellular distension and apoptosis. To exert cyclomodulatory and cytotoxic effects CDTs must be taken up from the host cell surface and transported intracellularly in a manner that ultimately results in localization of CdtB to the nucleus.

View Article and Find Full Text PDF

Haemophilus ducreyi resists the cytotoxic effects of human antimicrobial peptides (APs), including α-defensins, β-defensins, and the cathelicidin LL-37. Resistance to LL-37, mediated by the sensitive to antimicrobial peptide (Sap) transporter, is required for H. ducreyi virulence in humans.

View Article and Find Full Text PDF

Cytolethal distending toxins require components of the ER-associated degradation pathway for host cell entry.

PLoS Pathog

July 2014

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California, United States of America.

Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases. A subset of these toxins, the cytolethal distending toxins (CDTs), are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by allowing evasion of the immune system. CDTs are trafficked in a retrograde manner from the cell surface through the Golgi apparatus and into the endoplasmic reticulum (ER) before ultimately reaching the host cell nucleus.

View Article and Find Full Text PDF

Cellular interactions of the cytolethal distending toxins from Escherichia coli and Haemophilus ducreyi.

J Biol Chem

March 2013

Department of Microbiology, University of Illinois, Urbana, Illinois 61801; Institute for Genomic Biology, University of Illinois, Urbana, Illinois 61801. Electronic address:

The cytolethal distending toxins (CDTs) compose a subclass of intracellularly acting genotoxins produced by many Gram-negative pathogenic bacteria that disrupt the normal progression of the eukaryotic cell cycle. Here, the intoxication mechanisms of CDTs from Escherichia coli (Ec-CDT) and Haemophilus ducreyi (Hd-CDT), which share limited amino acid sequence homology, were directly compared. Ec-CDT and Hd-CDT shared comparable in vitro DNase activities of the CdtB subunits, saturable cell surface binding with comparable affinities, and the requirement for an intact Golgi complex to induce cell cycle arrest.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!