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One of the more common sexually transmitted diseases is chancroid, prevalent in tropical regions of the world but infiltrating more into Europe and the United States. It is not lethal in itself but has been linked with the transmission of HIV. Chancroid is caused by the pathogen Haemophilus ducreyi . The proteomes of several strains of this bacterium have been analyzed in an attempt to correlate the virulence of the strain with the protein content and the carbohydrate composition of the cell membranes. Chancroid (pronounced shang-kroid, from the French chancre, meaning tumour or cancer) is a genital ulcer disease that is spread by sexual contact. It affects both males and females but is more prevalent in males by a ratio of 3:1 up to 25:1. The disease presents itself by the appearance of painful open sores on the genitals, sometimes accompanied by swollen, tender lymph nodes in the groin. Symptoms in women are often less noticeable. The disease is caused by the Gram-negative bacterium Haemophilus ducreyi that enters the victim via abrasions or small cuts and the symptoms occur within a week of exposure. It can be treated with antibiotics, but the ulcers can persist for up to three months if not treated. For those who wish to learn more about this condition and see its effects, eMedicine has a great deal of additional information. In developing countries, chancroid is the cause of most genital ulcer diseases and the estimated worldwide incidence exceeds that of syphilis. It is endemic in Africa, Southeast Asia, Latin America, and the Caribbean. Periodic outbreaks occur in Western countries, the last one in the USA occurring in the late 1980s. Chancroid is not fatal but it has a strong association with the spread of the human immunodeficiency virus (HIV), the cause of AIDS. For this reason among others, it has been the subject of much study. For example, the complete non-redundant proteome of Haemophilus ducreyi has been determined. It is available at the European Bioinformatics Institute (EBI) where details of 1694 encoded proteins are held. In addition, several bacterial proteins have been identified as potent virulence factors. The outer membrane of H. ducreyi also contains many carbohydrate-type compounds called lipooligosaccharides (LOS) which may contribute to the infection process. In an effort to try and identify links between the virulence of the bacteria and the protein and LOS contents, researchers in the USA have compared eight different strains of the bacterium and their findings are reported in J. Proteome Res. 2003, 2, 523. They studied the proteomes of the various strains by standard methods, the LOS having been characterized in earlier work. Bradford Gibson, Karoline Scheffler and Deborah Post from the Buck Institute for Age Research in Novato, CA, with Arnold Falick and Steven Hall from Applied Biosystems and William Ray and Robert Munson, Jr. from the Columbus Children's Research Institute and The Ohio State University in Columbus, OH carried out the work. Both the soluble and insoluble protein fractions from whole cells were separated by two-dimensional SDS-PAGE and selected protein spots were cut out and digested on the gel with trypsin. The peptide mixtures obtained were analyzed by matrix-assisted laser-desorption/ionization mass spectrometry (MALDI MS). From 500-800 spots, more than 100 protein spots were analyzed which led to 122 distinct proteins being identified. Initially, the peptide masses were matched with the NCBI and Swiss-Prot databases for Haemophilus but only 12 proteins were identified this way, because there is no genome-wide sequence data for H. ducreyi in public databases. This was circumvented by using the new and partially annotated sequence genome of the closely related organism H. influenzae and proteins were identified by homology between the species. In general, there was very little difference in the proteomes between the strains of varying virulence. In addition, the composition of the LOS appeared to have little correlation with the proteome. The single exception to this conclusion involved an African strain of the bacterium (33921), which is a less virulent strain than the others. It had significant differences in the 2-D proteome map and is known to have a markedly different LOS composition. These preliminary studies were sufficient to begin a proteome database for H. ducreyi that will form the basis for further proteome studies. However, more research is required to correlate the protein differences with the virulence and the carbohydrate composition. Related Links:
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