Haemophilus ducreyi

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A Microbial Biorealm page on the genus Haemophilus ducreyi

Classification

Higher order taxa

Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales; Pasteurellaceae; [Others may be used. Use NCBI link to find]

Species

NCBI: Taxonomy

Coccobacillus ducreyi, Bacillus ulceris cancrosi, Haemophilus ducreyi

Description and significance

Haemophilus ducreyi causes the sexually transmitted disease, Chancroid. There has been renewed interest in this bacillus because of the close connections between Chancroid and Human Immunodeficiency Virus (HIV) infections (Spinola et al, 2002). It typically grows on the male genitalia and causes a painful shallow ulcer at the site of infection, however women can also get chancroid at a 1:3 ratio (Spinola et al, 2002). It is more common in African, Asian, and Latin American countries and is rarely seen in developed countries such as the US.

Haemophilus ducreyi was first described in 1889 by Auguste Ducrey The organism was isolated on artificial media a decade later but has remained difficult to isolate consistently. However novel methods of isolating these bacteria have been developed. It can grow well on a chocolate Agar supplemented with 1% Iso VitaleX and 5% sheep blood (Albritton, 1989). Oxygen and high levels of carbon dioxide are preferable, and it needs to be grown in blood clot tubes in a humid atmosphere. It was once thought H. ducreyi was related to other Haemophilus species, however it is barely related to commonly accepted haemophili (Spinola et al, 2002).

Genome structure

This bacterium consists of 1,698,955 base pairs and 1717 genes. It has a circular chromosome. There are 649,349 G+C base pairs, which accounts for 38.22% of the total base pairs. Also, 1,693 open reading frames were identified in this bacterium (NCBI). Only 5 plasmid profiles have been identified out of 342 strains of Haemophilus ducreyi, however the characteristics of these plasmids are still being studied.

Cell structure and metabolism

Haemophilus ducreyi is a gram-negative, rod-shaped, facultatively anaerobic, non-motile, pathogenic bacillus (Trees and Morse, 1995).

gram stain of H. ducreyi

Unlike other Haemophila, H. ducreyi is unable to synthesize heme because it lacks the enzyme ferro-chelatase, which is used to catalyze the synthesis of heme by inserting ferrous iron into protoporphyrin IX. Its main source of heme is from hemoglobin, which is observed to be acquired through cell invasion of the host. The process by which H. ducreyi takes in the hosts heme has been shown to be a "TonB- and TdhA-independent mechanism, possibly diffusion" (Thomas et al, 1998). Recent studies suggest that fimbria like protein (flp) found in H. ducreyi must be present for virulence. These proteins appear to allow H. ducreyi to properly bond in the host (Janowicz et al, 2011).

Some important molecules that are secreted by H. ducreyi include cytolethal distending toxin (CDT) and hemolysin (Cope et al, 1997). CDT is also secreted and could be the cause of the generation and slow healing of ulcers (Cortes-Bratti et al, 1999). The bacterium also causes the host to secrete Interleukin 8 (IL-8) and IL-6, potent chemoattractants for neutrophils. Virulence determinants have been difficult to identify because of the nature of H. ducreyi, however new techniques such as signature-tagged mutagenesis are being researched for properly identifying determinants. These techniques show promise and should improve understanding of H. ducreyi in future studies (Yeung et al, 2011). However it has also been suggested that virulence determinants of Haemophilus ducreyi are difficult to identify because what are thought to be clones are actually different species. This has resulted in the suggestion that there are two different classes of H. ducreyi that should be studied independently (Ricotta et al, 2011).

Pathology

electron micrograph of H. ducreyi

H. ducreyi infects cells by entering the skin through wounds and stimulating keratinocytes, fibroblasts, endothelial cells, or melanocytes to secrete IL-6 and IL-8. While bacteria is definitely transferred from lesions, it is also suggested that bacteria can be transferred before lesions appear (Spinola et al, 1996). IL-8 leads to polymorphonuclear leukocytes (PMN) and macrophage accumulation in epidermis and dermis. IL-6 leads to IL-2 and IL-2 expression in T-cells. Thus recruiting CD4 to the abrasions. Fibrin and collagen deposits are part of the wound, they repair and act as a matrix for the PMNs and macrophages. Lipoproteins and lipooligosaccharide (LOS) activate macrophages to make IL-12 and TNF-α which works with chemokines. IFN- γ, which is produced by T cells, and TNF- α allow keratinocytes to make IL-8 and other chemokines which amplify the process. Inflammatory cytokines and bacterial products migrate to lymph nodes where T cells naïve to H. ducreyi antigens are sensitized. Memory T-cells specific to H. ducreyi then go to the lesion. When PMN’s and macrophages fail to clear the organism type 1 immunity is sustained and its products continue to form. The products from type 1 immunity damage the skin, this is why chancroid is a type of immunopathogenesis. H. ducreyi also produces a cytotoxin that kills HeLa and HEp-2 cells (Cope et al, 1997).

Symptoms of chancroid start with a small bump that becomes an ulcer within a day of its appearance. The ulcer ranges between 1/8 to 2 inches in size, it is painful, and has irregular or ragged borders. The base is covered with grayish or yellowish material and it easily bleeds if traumatized. Ulcers most commonly form on the foreskin of the penis and on the groove behind the head of the penis (Albritton, 1989).

References

Albritton, W. "Biology of Haemophilus ducreyi". Microbiol Rev. 1989. p. 377–389.

Cope, L., Lumbley, S., Latimer, J., Klesney-Tait, J., Stevens, M., Johnson, L., Purven, M., Munson, R., Lagergard, T., Radolf, J., and Hansen, E. 1997. A diffusible cytotoxin of Hameophilus ducreyi. Proceedings of the National Academy of Sciences. 94: 4056-4061.

Cortes-Bratti, X, Chaves-Olarte, E, Lagergard, T, and Thelestam, M. 1999. The cytolethal distending toxin from the chancroid bacterium Haemophilus ducreyi induces cell-cycle arrest in the G2 phase. Journal of Clinical Investigation. 103: 107-115.

Janowicz, D, Cooney, S, Walsh, J, Baker, B, Katz, B, Fortney, K, Zqickl, B, Ellinger, S, and Munson, R. 2011. Expression of the Flp proteins by Haemophilus ducreyi is necessary for virulence in human volunteers. BioMed Central Microbiology. 11: 208.

Ricotta, E, Wang, N, Cutler, R, Lawrence, J, and Humphreys, T. 2011. Rapid Divergence of Two Classes of Haemophilus ducreyi. American Society for Microbiology. 10: 1128.

Spinola, S, Bauer M, and Munson, R. 2002. Immonopathogenesis of Haemophilus ducreyi Infection (Chancroid). American Society for Microbiology. 4: 1667-1676.

Thomas, CE, Olsen, B, and Elkins, C. 1998. Cloning and Characterization of tdhA, a locus encoding a TonB-dependent heme receptor from Haemophilus ducreyi. Infection and Immunity. 66: 4254-62.

Trees, D., Morse, S. 1995. Chancroid and Haemophilus ducreyi: an update. American Society for Microbiology. 8: 35-375.

Ward, C., Lumbley, S., Latimer, J., Cope L., and Hansen, E. "Haemophilus ducreyi Secretes a Filamentous Hemagglutinin-Like Protein". American Society for Microbiology. 1998.

Yeung, A, Cameron, DW, Desjardins, M, and Lee, BC. 2011. Use of signature-tagged mutagenesis to identify virulence determinants in Haemophilus ducreyi responsible for ulcer formation. Journal of Microbiological Methods. 84: 290-298.

Edited by Anthony Nguyen, student(s) of Rachel Larsen at UCSD.

Edited KMG

Edited by Megan Jones, student of Randolph-Macon College.