Publications

cytolethal distending toxin family members are differentially affected by alterations in host glycans and membrane cholesterol.	cytolethal distending toxins (cdts) are tripartite protein exotoxins produced by a diverse group of pathogenic gram-negative bacteria. based on their ability to induce dna damage, cell cycle arrest, and apoptosis of cultured cells, cdts are proposed to enhance virulence by blocking cellular division and/or directly killing epithelial and immune cells. despite the widespread distribution of cdts among several important human pathogens, our understanding of how these toxins interact with host cell ...	2010	20385557
role played by cd4+foxp3+ regulatory t cells in suppression of host responses to haemophilus ducreyi during experimental infection of human volunteers.	haemophilus ducreyi causes chancroid, a genital ulcer disease. among human volunteers, the majority of experimentally infected individuals fail to clear the infection and form pustules. here, we investigated the role played by cd4(+)foxp3(+) regulatory t (t(reg)) cells in the formation of pustules. in pustules, there was a significant enrichment of cd4(+)foxp3(+) t cells, compared with that in peripheral blood. the majority of lesional foxp3(+) t cells were cd4(+), cd25(+), cd127(lo/-), and ctla ...	2010	20443736
cervicovaginal fluid and semen block the microbicidal activity of hydrogen peroxide produced by vaginal lactobacilli.	h2o2 produced by vaginal lactobacilli is believed to protect against infection, and h2o2-producing lactobacilli inactivate pathogens in vitro in protein-free salt solution. however, cervicovaginal fluid (cvf) and semen have significant h2o2-blocking activity.	2010	20482854
immunization with the haemophilus ducreyi hemoglobin receptor hgba with adjuvant monophosphoryl lipid a protects swine from a homologous but not a heterologous challenge.	haemophilus ducreyi, the etiological agent of chancroid, has a strict requirement for heme, which it acquires from its only natural host, humans. previously, we showed that a vaccine preparation containing the native hemoglobin receptor hgba purified from h. ducreyi class i strain 35000hp (nhgbai) and administered with freund's adjuvant provided complete protection against a homologous challenge. in the current study, we investigated whether nhgbai dispensed with monophosphoryl lipid a (mpl), an ...	2010	20584974
activation of the cpxra system by deletion of cpxa impairs the ability of haemophilus ducreyi to infect humans.	haemophilus ducreyi must adapt to the environment of the human host to establish and maintain infection in the skin. bacteria generally utilize stress response systems, such as the cpxra two-component system, to adapt to hostile environments. cpxra is the only obvious two-component system contained in the h. ducreyi genome and negatively regulates the lspb-lspa2 operon, which encodes proteins that enable the organism to resist phagocytosis. we constructed an unmarked, in-frame h. ducreyi cpxa de ...	2010	20605985
detoxified haemophilus ducreyi cytolethal distending toxin and induction of toxin specific antibodies in the genital tract.	haemophilus ducreyi causes genital ulceration (chancroid), a sexually transmitted infection and still an important factor which contributes to the spread of hiv in developing countries. the bacterium produces a cytolethal distending toxin (hdcdt) causing cell cycle arrest and apoptosis/necrosis of human cells and contributes to the aggravation of ulcers. the aim of the study was to induce toxin-neutralizing antibodies in the genital tract of mice. repeated subcutaneous (sc) immunisations with 5- ...	2010	20609397
[import and local transmission of haemophilus ducreyi].	chancroid is a sexually transmitted disease characterized by painful ulcers with a soft margin, necrotic base and purulent exudate. previously, only sporadic, imported cases have been reported in denmark. the bacterium is difficult to culture and novel polymerase chain reaction (pcr)-based methods for direct demonstration of bacterial dna have facilitated rapid verification of the clinical diagnosis. we report two cases which demonstrate import and subsequent local transmission in denmark. in bo ...	2010	20654280
characterization of the cpxra regulon in haemophilus ducreyi.	the haemophilus ducreyi 35000hp genome encodes a homolog of the cpxra two-component cell envelope stress response system originally characterized in escherichia coli. cpxr, the cytoplasmic response regulator, was shown previously to be involved in repression of the expression of the lspb-lspa2 operon (m. labandeira-rey, j. r. mock, and e. j. hansen, infect. immun. 77:3402-3411, 2009). in the present study, the h. ducreyi cpxr and cpxa proteins were shown to closely resemble those of other well-s ...	2010	20805330
new plasmid tools for genetic analysis of actinobacillus pleuropneumoniae and other pasteurellaceae.	we have generated a set of plasmids, based on the mobilizable shuttle vector pmidg100, which can be used as tools for genetic manipulation of actinobacillus pleuropneumoniae and other members of the pasteurellaceae. a tandem reporter plasmid, pmc-tandem, carrying promoterless xyle and gfpmut3 genes downstream of a multiple-cloning site (mcs), can be used for identification of transcriptional regulators and conditions which favor gene expression from different cloned promoters. the ability to det ...	2009	19666733
aetiology of genital ulcer disease in female partners of male participants in a circumcision trial in uganda.	hiv acquisition is associated with herpes simplex virus type 2 (hsv-2) infection and genital ulcer disease (gud). three randomized control trials demonstrated that male circumcision significantly decreases hiv, hsv-2, human papillomavirus and self-reported gud among men. gud is also decreased among female partners of circumcised men, but it is unknown whether male circumcision status affects gud pathogens in female partners. for the evaluation of gud aetiology, two separate multiplex assays were ...	2009	19710342
localization of the domains of the haemophilus ducreyi trimeric autotransporter dsra involved in serum resistance and binding to the extracellular matrix proteins fibronectin and vitronectin.	resisting the bactericidal activity of naturally occurring antibodies and complement of normal human serum is an important element in the evasion of innate immunity by bacteria. in the gram-negative mucosal pathogen haemophilus ducreyi, serum resistance is mediated primarily by the trimeric autotransporter dsra. dsra also functions as an adhesin for the extracellular matrix proteins fibronectin and vitronectin and mediates attachment of h. ducreyi to keratinocytes. we sought to determine the dom ...	2009	19015257
advantages and pitfalls of the polymerase chain reaction in the diagnosis of esophageal ulcers in aids patients.	hiv-1-infected patients frequently have opportunistic esophageal infections which, when associated with severe immunodeficiency, can be attributed to unusual pathogens. the clinical presentation of several esophageal diseases is similar and the best method for a specific diagnosis of these patients has not been well defined. to evaluate the role of the polymerase chain reaction (pcr) in the etiologic definition of esophageal ulcers in hiv-1-infected patients, 96 esophageal biopsies from 79 hiv-1 ...	2009	19051024
evaluation of multiplex real-time pcr for detection of haemophilus ducreyi, treponema pallidum, herpes simplex virus type 1 and 2 in the diagnosis of genital ulcer disease in the rakai district, uganda.	to develop a real-time pcr assay that reliably and accurately detects the predominant sexually transmitted aetiological agents of genital ulcer disease (gud) (haemophilus ducreyi, treponema pallidum and herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2)) and to assess the use of real-time pcr diagnostic testing in a rural african field site.	2009	19066198
structural basis of heme binding in the cu,zn superoxide dismutase from haemophilus ducreyi.	the cu,zn superoxide dismutase from haemophilus ducreyi is characterized by the unique ability to bind heme at its dimer interface. here we report the high-resolution crystal structures of this protein in the heme-loaded (holo) and heme-free (apo) forms. heme is asymmetrically bound between the two enzyme subunits, where heme iron is coordinated by two histidine residues, his64 and his 124, provided by the two subunits. moreover, the binding of heme to the protein is ensured by stabilizing conta ...	2009	19103206
comparative proteomic analysis of the haemophilus ducreyi porin-deficient mutant 35000hp::p2ab.	haemophilus ducreyi is an obligate human pathogen and the causative agent of the sexually transmitted, genital ulcerative disease chancroid. the genome of strain 35000hp contains two known porin proteins, ompp2a and ompp2b. loss of ompp2a and ompp2b expression in the mutant 35000hp::p2ab resulted in no obvious growth defect or phenotype. comparison of outer membrane profiles indicated increased expression of the 58.5-kda chaperone, groel, in the porin-deficient mutant. a proteomics-based compari ...	2009	19103932
a novel mode of translocation for cytolethal distending toxin.	thermal instability in the toxin catalytic subunit may be a common property of toxins that exit the endoplasmic reticulum (er) by exploiting the mechanism of er-associated degradation (erad). the haemophilus ducreyi cytolethal distending toxin (hdcdt) does not utilize erad to exit the er, so we predicted the structural properties of its catalytic subunit (hdcdtb) would differ from other er-translocating toxins. here, we document the heat-stable properties of hdcdtb which distinguish it from othe ...	2009	19118582
a fibrinogen-binding lipoprotein contributes to the virulence of haemophilus ducreyi in humans.	a gene expression study of haemophilus ducreyi identified the hypothetical lipoprotein hd0192, renamed here "fibrinogen binder a" (fgba), as being preferentially expressed in vivo. to test the role played by fgba in virulence, an isogenic fgba mutant (35000hpfgba) was constructed using h. ducreyi 35000hp, and 6 volunteers were experimentally infected with 35000hp or 35000hpfgba. the overall pustule-formation rate was 61.1% at parent sites and 22.2% at mutant sites (p = .019). papules were signif ...	2009	19199547
haemophilus ducreyi detection by polymerase chain reaction in oesophageal lesions of hiv patients.	hiv patients frequently have opportunistic oesophageal infections. we report haemophilus ducreyi genetic material detected by polymerase chain reaction in biopsies of oesophageal lesions in three hiv-1-infected patients. this finding may be an indication of its aetiopathological role in oesophageal lesions of hiv patients.	2009	19304967
immunogenic and adjuvant properties of haemophilus ducreyi lipooligosaccharides.	haemophilus ducreyi, the chancroid-causing bacterium, produces lipooligosaccharides (hdlos) that comprise 5-11 partially sialylated monosaccharides. subcutaneous immunisation of mice with 5 microg of hdlos purified from h. ducreyi strains 4438 and 7470 induced high levels of anti-hdlos igg. the antibody responses displayed t-cell-independent features, and were dependent upon toll-like receptor 4/myd88 signalling pathways as demonstrated using knockout mice. the immunogenicity of hdlos was found ...	2009	19397884
experimental infection of human volunteers with haemophilus ducreyi: fifteen years of clinical data and experience.	haemophilus ducreyi causes chancroid, which facilitates transmission of human immunodeficiency virus type 1. to better understand the biology of h. ducreyi, we developed a human inoculation model. in the present article, we describe clinical outcomes for 267 volunteers who were infected with h. ducreyi. there was a relationship between papule formation and estimated delivered dose. the outcome (either pustule formation or resolution) of infected sites for a given subject was not independent; the ...	2009	19432549
regulation of expression of the haemophilus ducreyi lspb and lspa2 proteins by cpxr.	the lspa1, lspa2, and lspb proteins of haemophilus ducreyi comprise a two-partner secretion system that has been shown to be necessary for h. ducreyi to inhibit phagocytosis by immune cells in vitro. inactivation of lspa1 resulted in increased levels of lspa2, suggesting that these two proteins are differentially controlled (c. j. ward et al., infect. immun. 71:2478-2486, 2003). expression of lspa2 but not lspa1 was shown to be both growth phase dependent and affected by the presence of fetal ca ...	2009	19451237
an immunogenic, surface-exposed domain of haemophilus ducreyi outer membrane protein hgba is involved in hemoglobin binding.	hgba is the sole tonb-dependent receptor for hemoglobin (hb) acquisition of haemophilus ducreyi. binding of hb to hgba is the initial step in heme acquisition from hb. to better understand this step, we mutagenized hgba by deletion of each of the 11 putative surface-exposed loops and expressed each of the mutant proteins in trans in host strain h. ducreyi fx547 hgba. all mutant proteins were expressed, exported, and detected on the surface by anti-hgba immunoglobulin g (igg). deletion of sequenc ...	2009	19451245
identification of iron-acquisition proteins of avibacterium paragallinarum.	when avibacterium paragallinarum reference strain 0083 (serovar a) was grown in an iron-restricted culture medium, the expression of the 60, 68 and 93 kda outer membrane proteins increased as compared with normal media. sera of chickens experimentally infected with av. paragallinarum recognized these iron-restriction induced proteins, suggesting their expression in vivo. the three outer membrane proteins were identified as transferrin receptor and iron transport proteins by mass spectroscopy and ...	2009	19468937
[image of the month. combined chancre, a soft chancroid and a syphilitic chancre].		2009	19514534
inactivation of the haemophilus ducreyi luxs gene affects the virulence of this pathogen in human subjects.	haemophilus ducreyi 35000hp contains a homologue of the luxs gene, which encodes an enzyme that synthesizes autoinducer 2 (ai-2) in other gram-negative bacteria. h. ducreyi 35000hp produced ai-2 that functioned in a vibrio harveyi-based reporter system. a h. ducreyi luxs mutant was constructed by insertional inactivation of the luxs gene and lost the ability to produce ai-2. provision of the h. ducreyi luxs gene in trans partially restored ai-2 production by the mutant. the luxs mutant was compa ...	2009	19552526
mechanism of human natural killer cell activation by haemophilus ducreyi.	the role of natural killer (nk) cells in the host response to haemophilus ducreyi infection is unclear. in pustules obtained from infected human volunteers, there was an enrichment of cd56bright nk cells bearing the activation markers cd69 and hla-dr, compared with peripheral blood. to study the mechanism by which h. ducreyi activated nk cells, we used peripheral blood mononuclear cells from uninfected volunteers. h. ducreyi activated nk cells only in the presence of antigen-presenting cells. h. ...	2009	19572804
chancroid in an hiv-negative woman in the midwestern united states.		2009	19926434
predicted b-cell epitopes on 18 kda antigen of haemophilus ducreyi.		2008	19172013
[utility of molecular biology techniques in the diagnosis of sexually transmitted diseases and genital infections].	historically, the diagnosis of sexually transmitted diseases (stds) has been difficult. the introduction of molecular biology techniques in microbiological diagnosis and their application to non-invasive samples has produced significant advances in the diagnosis of these diseases. overall, detection of neisseria gonorrhoeae by molecular biology techniques provides a presumptive diagnosis and requires confirmation by culture in areas with a low prevalence. for chlamydia trachomatis infections, th ...	2008	19195446
a role for haemophilus ducreyi cu,znsod in resistance to heme toxicity.	the cu,zn superoxide dismutase (cu,znsod) from haemophilus ducreyi is the only enzyme of this class which binds a heme molecule at its dimer interface. to explore the role of the enzyme in this heme-obligate bacterium, a sodc mutant was created by insertional inactivation. no difference in growth rate was observed during heme limitation. in contrast, under heme rich conditions growth of the sodc mutant was impaired compared to the wild type strain. this growth defect was abolished by supplementa ...	2008	17704897
chancroid and human immunodeficiency virus infection--a review.		2008	18173591
[microbiological diagnosis of sexually-transmitted infection (2007)].	sexually transmitted infections (stis) constitute an important world-wide public health problem. the use of sensitive and specific laboratory methods for diagnosing this condition is crucial to reduce the transmission and sequelae of sti. the present review describes current microbiological methods for the diagnosis of stis. neisseria gonorrhoeae and chlamydia trachomatis are the pathogens most frequently involved in urethral and cervical infection. culture continues to be the gold standard for ...	2008	18208764
outer membrane protein dsra is the major fibronectin-binding determinant of haemophilus ducreyi.	the ability to bind extracellular matrix proteins is a critical virulence determinant for skin pathogens. haemophilus ducreyi, the etiological agent of the genital ulcer disease chancroid, binds extracellular matrix components, including fibronectin (fn). we investigated h. ducreyi fn binding and report several important findings about this interaction. first, fn binding by h. ducreyi was greatly increased in bacteria grown on heme and almost completely inhibited by hemoglobin. second, wild-type ...	2008	18212073
killing of neisseria gonorrhoeae, streptococcus agalactiae (group b streptococcus), haemophilus ducreyi, and vaginal lactobacillus by 3-o-octyl-sn-glycerol.	the microbicide candidate octylglycerol inactivates sexually transmitted bacterial pathogens at concentrations which spare normal vaginal flora (lactobacillus). standard minimum microbicidal concentration assays and time-kill assays revealed the drug concentrations and times required for inactivation. octylglycerol concentrations must exceed the binding capacity of any human serum albumin to be effective.	2008	18227178
identification of haemophilus ducreyi genes expressed during human infection.	to identify haemophilus ducreyi transcripts that are expressed during human infection, we used selective capture of transcribed sequences (scots) with rna isolated from pustules obtained from three volunteers infected with h. ducreyi, and with rna isolated from broth-grown bacteria used to infect volunteers. with scots, competitive hybridization of tissue-derived and broth-derived sequences identifies genes that may be preferentially expressed in vivo. among the three tissue specimens, we identi ...	2008	18375807
modelling the cost per ulcer treated of incorporating episodic treatment for hsv-2 into the syndromic algorithm for genital ulcer disease.	the proportion of genital ulcer disease (gud) due to herpes simplex virus type-2 (hsv-2) has increased in sub-saharan africa. the most recent 2003 who syndromic gud algorithm includes antiviral treatment for hsv-2 for anyone with "typical" symptoms/signs, and suggests that all gud patients receive treatment for hsv-2 in settings where hsv-2 gud aetiology is greater than 30%. the previous algorithm (1994) only targeted haemophilus ducreyi (hd) and treponema pallidum (tp).	2008	18385226
cutaneous chancroid in a visitor from vanuatu.	a 23-year-old woman from vanuatu presented to an australian hospital with a 3-week history of a non-healing ulcer on the lower leg. a swab was submitted for a multiplex polymerase chain reaction designed to investigate genital ulcerative conditions. haemophilus ducreyi was detected and the gene product was subsequently sequenced, confirming the diagnosis of cutaneous chancroid. the lesion responded to intramuscular benzathine penicillin. this report adds further evidence that cutaneous chancroid ...	2008	18412810
the enterobacterial common antigen-like gene cluster of haemophilus ducreyi contributes to virulence in humans.	haemophilus ducreyi 35000hp contains a cluster of homologues of genes required for the synthesis of enterobacterial common antigen (eca), suggesting that h. ducreyi may express a putative eca-like glycoconjugate. weca initiates the synthesis of eca by transferring n-acetylglucosamine to undecaprenyl-p, to form lipid i. a weca mutant (35000hpweca) was constructed, and 5 volunteers were inoculated at 3 sites with fixed doses of 35000hp on one arm and at 3 sites with varying doses of 35000hpweca on ...	2008	18422457
ultrafast heme-residue bond formation in six-coordinate heme proteins: implications for functional ligand exchange.	a survey is presented of picosecond kinetics of heme-residue bond formation after photolysis of histidine, methionine, or cysteine, in a broad range of ferrous six-coordinate heme proteins. these include human neuroglobin, a bacterial heme-binding superoxide dismutase (sod), plant cytochrome b 559, the insect nuclear receptor e75, horse heart cytochrome c and the heme domain of the bacterial sensor protein dos. we demonstrate that the fastest and dominant phase of binding of amino acid residues ...	2008	18454557
evaluation of the repertoire of the tonb-dependent receptors of haemophilus ducreyi for their role in virulence in humans.	haemophilus ducreyi contains 3 tonb-dependent receptors: the hemoglobin receptor hgba, which is required for virulence in humans; the heme receptor tdha; and an uncharacterized conserved hypothetical protein tdx (hd0646). a double tdx/tdha mutant (fx527) was constructed on the background of a human-passaged variant of strain 35000 (35000hp). six volunteers were infected with 35000hp at 3 sites on one arm and with fx527 at 3 sites on the other. the pustule formation rate was 55.6% (95% confidence ...	2008	18462159
in vivo virulence properties of bacterial cytolethal-distending toxin.	multiple pathogenic gram-negative bacteria produce cytolethal-distending toxins (cdts). cdt is typically composed of three subunits: the catalytic subunit cdtb has dnase i-like activity, whereas cdta and cdtc are binding proteins for delivering cdtb into target cells. translocation of cdtb to the nucleus induces genotoxic effects on host dna, triggering dna repair cascades that lead to cell cycle arrest and eventual cell death. several lines of evidence indicate that this toxin contributes to th ...	2008	18489725
copper and zinc binding properties of the n-terminal histidine-rich sequence of haemophilus ducreyi cu,zn superoxide dismutase.	the cu,zn superoxide dismutase (cu,znsod) isolated from haemophilus ducreyi possesses a his-rich n-terminal metal binding domain, which has been previously proposed to play a copper(ii) chaperoning role. to analyze the metal binding ability and selectivity of the histidine-rich domain we have carried out thermodynamic and solution structural analysis of the copper(ii) and zinc(ii) complexes of a peptide corresponding to the first 11 amino acids of the enzyme (h(2)n-hgdhmhnhdtk-oh, l). this pepti ...	2008	18565588
haemophilus ducreyi lspa proteins are tyrosine phosphorylated by macrophage-encoded protein tyrosine kinases.	the lspa proteins (lspa1 and lspa2) of haemophilus ducreyi are necessary for this pathogen to inhibit the phagocytic activity of macrophage cell lines, an event that can be correlated with a reduction in the level of active src family protein tyrosine kinases (ptks) in these eukaryotic cells. during studies investigating this inhibitory mechanism, it was discovered that the lspa proteins themselves were tyrosine phosphorylated after wild-type h. ducreyi cells were incubated with macrophages. lsp ...	2008	18678665
bacterial cmp-sialic acid synthetases: production, properties, and applications.	sialic acids are abundant nine-carbon sugars expressed terminally on glycoconjugates of eukaryotic cells and are crucial for a variety of cell biological functions such as cell-cell adhesion, intracellular signaling, and in regulation of glycoproteins stability. in bacteria, n-acetylneuraminic acid (neu5ac) polymers are important virulence factors. cytidine 5'-monophosphate (cmp)-n-acetylneuraminic acid synthetase (css; ec 2.7.7.43), the key enzyme that synthesizes cmp-n-acetylneuraminic acid, t ...	2008	18716769
cytolethal distending toxin upregulates rankl expression in jurkat t-cells.	cytolethal distending toxin, a bacterial exotoxin produced by a number of gram-negative species, causes growth arrest and morphological alterations in host cells. among these species are haemophilus ducreyi, the etiological agent of chancroid, and the periodontal pathogen aggregatibacter actinomycetemcomitans, highly implicated in localized aggressive periodontitis. cdt induces receptor activator of nf-kappab ligand (rankl) expression in periodontal fibroblasts, the key bone-resorbing cytokine. ...	2008	18754324
complete genome sequence of haemophilus somnus (histophilus somni) strain 129pt and comparison to haemophilus ducreyi 35000hp and haemophilus influenzae rd.	haemophilus somnus can be either a commensal of bovine mucosal surfaces or an opportunistic pathogen. pathogenic strains of h. somnus are a significant cause of systemic disease in cattle. we report the genome sequence of h. somnus 129pt, a nonpathogenic commensal preputial isolate, and the results of a genome-wide comparative analysis of h. somnus 129pt, haemophilus influenzae rd, and haemophilus ducreyi 35000hp. we found unique genes in h. somnus 129pt involved in lipooligosaccharide biosynthe ...	2007	17172329
formaldehyde treatment increases the immunogenicity and decreases the toxicity of haemophilus ducreyi cytolethal distending toxin.	haemophilus ducreyi cytolethal distending toxin (hdcdt) is a tripartite ab toxin, which causes dna damage in affected cells. we investigated the effects of formaldehyde on the chemical, biological, and immunological properties of the hdcdt complex, which was purified by immobilizing the glutathione s-transferase (gst)-cdtb fusion protein, followed by binding of the cdta and cdtc recombinant proteins. the hdcdt was treated with increasing concentrations of formaldehyde in the presence of lysine. ...	2007	17289219
rapid, accurate, computational discovery of rho-independent transcription terminators illuminates their relationship to dna uptake.	in many prokaryotes, transcription of dna to rna is terminated by a thymine-rich stretch of dna following a hairpin loop. detecting such rho-independent transcription terminators can shed light on the organization of bacterial genomes and can improve genome annotation. previous computational methods to predict rho-independent terminators have been slow or limited in the organisms they consider.	2007	17313685
[genital ulcers caused by sexually transmitted diseases: current therapies, diagnosis and their relevance in hiv pandemy].	the sexual transmitted pathogens associated with genital ulcers are treponema pallidum, haemophilus ducreyi, calymmatobacterium granulomatis, chlamydia trachomatis and herpes simplex virus type 1 or 2. although geographic differences still exist, herpetic infections prevalence is growing worldwide as the most frequent ulcerative sexual transmitted disease. the failure of the many different used guidelines in achieving a sustained reduction in the number of new cases, in particular the who syndro ...	2007	17328851
experimental infection with haemophilus ducreyi in persons who are infected with hiv does not cause local or augment systemic viral replication.	we infected 11 hiv-seropositive volunteers whose cd4(+) cell counts were >350 cells/ microl (7 of whom were receiving antiretrovirals) with haemophilus ducreyi. the papule and pustule formation rates were similar to those observed in hiv-seronegative historical control subjects. no subject experienced a sustained change in cd4(+) cell count or hiv rna level. the cellular infiltrate in biopsy samples obtained from the hiv-seropositive and hiv-seronegative subjects did not differ with respect to t ...	2007	17436224
haemophilus ducreyi causing chronic skin ulceration in children visiting samoa.	chancroid is a sexually transmitted infection associated with genital ulceration and lymphadenopathy caused by haemophilus ducreyi. localized skin infections, in the absence of genital lesions, have not been previously reported. we report 3 cases of lower limb ulceration in children caused by h. ducreyi and postulate that h. ducreyi may be a previously unrecognized cause of chronic skin ulceration.	2007	17443459
[chancroid].	chancroid is caused by the bacterium haemophilus ducreyi. it is a sexually transmitted disease causing a soft chancre with a necrotic base and purulent exudate. the incidence of this illness is very low in denmark and is probably underestimated. the bacterium is very fragile in transport, and culture is often negative. the chance of demonstrating the bacterium is greatly enhanced by the use of molecular techniques. in this case, we report on a specific pcr test for h. ducreyi that was used to es ...	2007	17553398
herpes simplex virus infection and genital ulcer disease among patients with sexually transmitted infections in dar es salaam, tanzania.	the relative importance of haemophilus ducreyi and treponema pallidum in genital ulcer disease in africa has decreased recently, whereas that of herpes simplex virus (hsv) type 2 has increased. we analysed 301 lesional specimens from tanzanian patients with genital ulcer disease for the presence of h. ducreyi, t. pallidum and hsv-1/hsv-2 by performing a separate pcr for each pathogen. infectious agents were detected in 211 (70%) of the cases. a single pathogen was found in 191 samples and two or ...	2007	17598041
haemophilus ducreyi is resistant to human antimicrobial peptides.	we examined the susceptibility of haemophilus ducreyi to antimicrobial peptides likely to be encountered in vivo during human infection. h. ducreyi was significantly more resistant than escherichia coli to the bactericidal effects of all peptides tested. class i and ii h. ducreyi strains exhibited similar levels of resistance to antimicrobial peptides.	2007	17620373
possible reasons for an increase in the proportion of genital ulcers due to herpes simplex virus from a cohort of female bar workers in tanzania.	to determine trends in the prevalence and aetiological distribution of genital ulcer syndrome (gus) in a cohort of female bar workers and to assess factors associated with these trends.	2007	16971402
identification of genes involved in the expression of atypical lipooligosaccharide structures from a second class of haemophilus ducreyi.	haemophilus ducreyi is a gram-negative bacterium that is the causative agent of chancroid. strain 35000hp has been well characterized and is representative of the majority of h. ducreyi strains. strain 35000hp produces a lipooligosaccharide (los) that contains d-glycero-d-manno-heptose in the main oligosaccharide chain extension; the lbgb gene has been shown to encode the dd-heptosyltransferase. the lbgb gene is found in a gene cluster together with the lbga gene, which encodes for the galactosy ...	2007	17030566
dysregulated immune profiles for skin and dendritic cells are associated with increased host susceptibility to haemophilus ducreyi infection in human volunteers.	in experimentally infected human volunteers, the cutaneous immune response to haemophilus ducreyi is orchestrated by serum, polymorphonuclear leukocytes, macrophages, t cells, and myeloid dendritic cells (dc). this response either leads to spontaneous resolution of infection or progresses to pustule formation, which is associated with the failure of phagocytes to ingest the organism and the presence of th1 and regulatory t cells. in volunteers who are challenged twice, some subjects form at leas ...	2007	17893130
haemophilus ducreyi partially activates human myeloid dendritic cells.	dendritic cells (dc) orchestrate innate and adaptive immune responses to bacteria. how haemophilus ducreyi, which causes genital ulcers and regional lymphadenitis, interacts with dc is unknown. h. ducreyi evades uptake by polymorphonuclear leukocyte and macrophage-like cell lines by secreting lspa1 and lspa2. many h. ducreyi strains express cytolethal distending toxin (cdt), and recombinant cdt causes apoptosis of dc in vitro. here, we examined interactions between dc and h. ducreyi 35000hp, whi ...	2007	17923525
evidence that the cytolethal distending toxin locus was once part of a genomic island in the periodontal pathogen aggregatibacter (actinobacillus) actinomycetemcomitans strain y4.	the authors have previously shown that the periodontal pathogen aggregatibacter (formerly actinobacillus) actinomycetemcomitans y4 contains an operon for a genotoxin known as the cytolethal distending toxin (cdt). the cdt locus in strain y4 is flanked by remnants of heterologous plasmid and integrase sequences. in this study, the dna sequence immediately downstream from the cdt locus on the y4 chromosome was examined. the extended sequence contained a region that had all the characteristics of a ...	2007	17965355
the hd0053 gene of haemophilus ducreyi encodes an alpha2,3-sialyltransferase.	haemophilus ducreyi is a gram-negative bacterium that causes chancroid, a sexually transmitted genital ulcer disease. different lipooligosaccharide (los) structures have been identified from h. ducreyi strain 35000, including those sialylated glycoforms. surface los of h. ducreyi is considered an important virulence factor that is involved in ulcer formation, cell adhesion, and invasion of host tissue. gene hd0686 of h. ducreyi, designated lst (for lipooligosaccharide sialyltransferase), was ide ...	2007	17662691
proposed second class of haemophilus ducreyi strains show altered protein and lipooligosaccharide profiles.	haemophilus ducreyi is the etiologic agent of chancroid, a sexually transmitted genital ulcer disease. previously we have shown that the protein profiles and lipooligosaccharide (los) structures from various strains of h. ducreyi are generally well conserved. previous studies have demonstrated that at least one strain, 33921, has a variant protein profile and los structure. in this study, both the whole cell lysate and the membrane proteins from strain 33921 were further examined and compared to ...	2007	17676659
the contribution of cytolethal distending toxin to bacterial pathogenesis.	cytolethal distending toxin (cdt) is a bacterial toxin that initiates a eukaryotic cell cycle block at the g2 stage prior to mitosis. cdt is produced by a number of bacterial pathogens including: campylobacter species, escherichia coli, salmonella enterica serovar typhi, shigella dystenteriae, enterohepatic helicobacter species, actinobacillus actinomycetemcomitans (the cause of aggressive periodontitis), and haemophilus ducreyi (the cause of chancroid). the functional toxin is composed of three ...	2006	17123907
[chancroid].		2006	17146895
chancroid.		2006	17151046
the genome sequence of mannheimia haemolytica a1: insights into virulence, natural competence, and pasteurellaceae phylogeny.	the draft genome sequence of mannheimia haemolytica a1, the causative agent of bovine respiratory disease complex (brdc), is presented. strain atcc baa-410, isolated from the lung of a calf with brdc, was the dna source. the annotated genome includes 2,839 coding sequences, 1,966 of which were assigned a function and 436 of which are unique to m. haemolytica. through genome annotation many features of interest were identified, including bacteriophages and genes related to virulence, natural comp ...	2006	17015664
molecular characterization of haemophilus ducreyi isolates from different geographical locations.	the technique of random amplified polymorphic dna (rapd) was adapted and optimized to study haemophilus ducreyi isolates. a panel of 43 strains isolated from chancroid patients from different countries in africa, europe, north america, and asia were characterized. the strains were also studied with respect to lipooligosaccharide (los) migration and immunoblotting patterns and the presence of cytolethal distending toxin genes. the rapd method with the opj20 primer generated nine banding patterns ...	2006	16390960
expression of ompp2a and ompp2b is not required for pustule formation by haemophilus ducreyi in human volunteers.	haemophilus ducreyi express two porin proteins, termed ompp2a and ompp2b. to test whether expression of ompp2a and ompp2b was necessary for virulence in humans, eight volunteers were experimentally infected with the parent (35000hp) in one arm and a double ompp2a ompp2b mutant (35000hp::p2ab) in the other arm. the pustule formation rates were 58.3% (95% ci, 33.2-83.5%) for the parent and 41.7% (95% ci, 19.3-64.0%) for the mutant (p=0.25). biopsy of 35000hp and 35000hp::p2ab-infected sites yielde ...	2006	16426809
cytolethal distending toxin generates cell death by inducing a bottleneck in the cell cycle.	cytolethal distending toxin (cdt) is a bacterial protein that is widely distributed among gram-negative bacteria including escherichia coli, campylobacter spp., enterohepatic helicobacter spp., actinobacillus actinomycetemcomitans and haemophilus ducreyi. in vitro studies demonstrated that it is able to stop proliferation of various cell lines. the toxin is composed of three subunits designated cdts a, b and c. the b subunit targets the eukaryotic dna and triggers a signalling pathway involving ...	2006	16427513
a dlta mutant of haemophilus ducreyi is partially attenuated in its ability to cause pustules in human volunteers.	haemophilus ducreyi produces two outer membrane proteins, called dlta (h. ducreyi lectin a) and dsra (h. ducreyi serum resistance a), that contribute to the ability of the organism to evade complement-mediated serum killing. in contrast to their isogenic parent strain, 35000hp, the dsra mutant fx517 exhibits 0% survival in 50% normal human serum and the dlta mutant fx533 exhibits 23% survival. compared to 35000hp, fx517 does not cause pustule formation in human volunteers. to test whether dlta w ...	2006	16428791
variation of loop sequence alters stability of cytolethal distending toxin (cdt): crystal structure of cdt from actinobacillus actinomycetemcomitans.	cytolethal distending toxin (cdt) secreted by actinobacillus actinomycetemcomitans induces cell cycle arrest of cultured cells in the g2 phase. the crystal structure of the natural form of a. actinomycetemcomitans dct (acdt) has been determined at 2.4 a resolution. acdt is a heterotrimer consisting of the three subunits, acdta, acdtb, and acdtc. two crystallographically independent acdts form a dimer through interactions of the acdtb subunits. the primary structure of acdt has 94.3% identity wit ...	2006	16434747
immunization with the haemophilus ducreyi hemoglobin receptor hgba protects against infection in the swine model of chancroid.	the etiologic agent of chancroid is haemophilus ducreyi. to fulfill its obligate requirement for heme, h. ducreyi uses two tonb-dependent receptors: the hemoglobin receptor (hgba) and a receptor for free heme (tdha). expression of hgba is necessary for h. ducreyi to survive and initiate disease in a human model of chancroid. in this study, we used a swine model of h. ducreyi infection to demonstrate that an experimental hgba vaccine efficiently prevents chancroid, as determined by several parame ...	2006	16552053
male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta-analysis.	male circumcision is associated with reduced risk of hiv infection. this may be partly because of a protective effect of circumcision on other sexually transmitted infections (sti), especially those causing genital ulcers, but evidence for such protection is unclear. our objective was to conduct a systematic review and meta-analyses of the associations between male circumcision and infection with herpes simplex virus type 2 (hsv-2), treponema pallidum, or haemophilus ducreyi.	2006	16581731
detection and discrimination of herpes simplex viruses, haemophilus ducreyi, treponema pallidum, and calymmatobacterium (klebsiella) granulomatis from genital ulcers.	genital ulcer disease (gud) is commonly caused by pathogens for which suitable therapies exist, but clinical and laboratory diagnoses may be problematic. this collaborative project was undertaken to address the need for a rapid, economical, and sensitive approach to the detection and diagnosis of gud using noninvasive techniques to sample genital ulcers.	2006	16619156
expression of haemophilus ducreyi collagen binding outer membrane protein ncaa is required for virulence in swine and human challenge models of chancroid.	haemophilus ducreyi, the etiologic agent of the sexually transmitted genital ulcer disease chancroid, has been shown to associate with dermal collagen fibers within infected skin lesions. here we describe ncaa, a previously uncharacterized outer membrane protein that is important for h. ducreyi collagen binding and host colonization. an h. ducreyi strain lacking the ncaa gene was impaired in adherence to type i collagen but not fibronectin (plasma or cellular form) or heparin. the mutation had n ...	2006	16622201
localization of haemophilus ducreyi in naturally acquired chancroidal ulcers.	haemophilus ducreyi causes the sexually transmitted genital ulcer disease chancroid. in human inoculation experiments, bacteria colocalize with neutrophils and macrophages but remain extracellular. the organism also colocalizes with collagen and fibrin but not with keratinocytes, fibroblasts, laminin, or fibronectin. these relationships are established by 48 h postinoculation and persist through the pustular stage of disease. to extend these observations to the ulcerative stage of disease, and t ...	2006	16872858
binding of haemophilus ducreyi to carbohydrate receptors is mediated by the 58.5-kda groel heat shock protein.	the bacterium haemophilus ducreyi causes the sexually transmitted disease chancroid, which is characterized by the appearance of mucocutaneous, persistent ulcers on the external genitals. to identify carbohydrate receptors that mediate the attachment of this pathogen to host cells, we investigated the binding of 35s-methionine-labeled h. ducreyi strains to a panel of defined glycosphingolipids that were separated on thin layer chromatography plates. h. ducreyi bound to lactosylceramide, gangliot ...	2006	16880000
role of n-acetylglucosamine within core lipopolysaccharide of several species of gram-negative bacteria in targeting the dc-sign (cd209).	our recent studies have shown that the dendritic cell-specific icam nonintegrin cd209 (dc-sign) specifically binds to the core lps of escherichia coli k12 (e. coli), promoting bacterial adherence and phagocytosis. in this current study, we attempted to map the sites within the core lps that are directly involved in lps-dc-sign interaction. we took advantage of four sets of well-defined core lps mutants, which are derived from e. coli, salmonella enterica serovar typhimurium, neisseria gonorrhoea ...	2006	16951363
comparative structure-function analysis of cytolethal distending toxins.	cytolethal distending toxins (cdts) constitute a family of bacterial proteins that enter eukaryotic cells with genotoxic activity leading to cell cycle arrest and apoptosis. cdts are widespread, having been found in a variety of gram-negative pathogens with a broad tissue tropism. the recently determined crystal structure of the haemophilus ducreyi cdt provides a powerful starting point for analysis of the structure and function in this toxin family. in this study, we apply comparative modeling ...	2006	16304641
characterization of point mutations in the cdta gene of the cytolethal distending toxin of actinobacillus actinomycetemcomitans.	the cdt is a family of gram-negative bacterial toxins that typically arrest eukaryotic cells in the g0/g1 or g2/m phase of the cell cycle. the toxin is a heterotrimer composed of the cdta, cdtb and cdtc gene products. although it has been shown that the cdta protein subunit binds to cells in culture and in an enzyme-linked immunosorbent assay (celisa) the precise mechanisms by which cdta interacts with cdtb and cdtc has not yet been clarified. in this study we employed a random mutagenesis strat ...	2005	16313618
the cytolethal distending toxin induces receptor activator of nf-kappab ligand expression in human gingival fibroblasts and periodontal ligament cells.	actinobacillus actinomycetemcomitans is associated with localized aggressive periodontitis, a disease characterized by rapid loss of the alveolar bone surrounding the teeth. receptor activator of nf-kappab ligand (rankl) and osteoprotegerin (opg) are two molecules that regulate osteoclast formation and bone resorption. rankl induces osteoclast differentiation and activation, whereas opg blocks this process by acting as a decoy receptor for rankl. the purpose of this study was to investigate the ...	2005	15618171
cloning and sequencing of a genomic island found in the brazilian purpuric fever clone of haemophilus influenzae biogroup aegyptius.	a genomic island was identified in the haemophilus influenzae biogroup aegyptius brazilian purpuric fever (bpf) strain f3031. this island, which was also found in other bpf isolates, could not be detected in non-bpf biogroup aegyptius strains or in nontypeable or typeable h. influenzae strains, with the exception of a region present in the type b eagan strain. this 34,378-bp island is inserted, in reference to h. influenzae rd kw20, within a choline transport gene and contains a mosaic structure ...	2005	15784532
haemophilus ducreyi outer membrane determinants, including dsra, define two clonal populations.	the haemophilus ducreyi outer membrane component dsra (for ducreyi serum resistance a) is necessary for complete resistance to normal human serum (nhs). when dsra expression in 19 temporally and geographically diverse clinical isolates of h. ducreyi was examined by western blotting, 5 of the strains expressed a different immunotype of the dsra protein (dsra(ii)) than the well-characterized prototypical strain 35000hp (dsra(i)). the predicted dsra proteins expressed by the dsra(ii) strains were 1 ...	2005	15784585
improving the accuracy of syndromic diagnosis of genital ulcer disease in malawi.	objectives/goal: most resource-poor settings rely on syndromic criteria to diagnose genital ulcer disease (gud). however, the etiologic pathogens of gud vary temporally and geographically, and current criteria may not reflect changes in the prevalence of specific pathogens.	2005	15788921
induction of apoptosis/necrosis in various human cell lineages by haemophilus ducreyi cytolethal distending toxin.	we investigated the impact of highly purified haemophilus ducreyi cytolethal distending toxin (hdcdt) on the apoptosis and necrosis of various human cells; including myeloid cells, epithelial cells, keratinocytes, and primary fibroblasts. the levels of apoptosis and necrosis induced in these cells were compared to those induced by hdcdt in human t cells and in the jurkat t cell line. levels of caspase-3 activity were measured, and membrane changes like phosphatidylserine (ps) translocation was e ...	2005	15804526
characterization of a cluster of three glycosyltransferase enzymes essential for moraxella catarrhalis lipooligosaccharide assembly.	moraxella catarrhalis isolates express lipooligosaccharide (los) molecules on their surface, which share epitopes similar to that of the neisseria and haemophilus species. these common los epitopes have been implicated in various steps of pathogenesis for the different organisms. in this study, a cluster of three los glycosyltransferase genes (lgt) were identified in m. catarrhalis 7169, a strain that produces a serotype b los. mutants in these glycosyltransferase genes were constructed, and the ...	2005	15838019
rifaximin, a peculiar rifamycin derivative: established and potential clinical use outside the gastrointestinal tract.	rifaximin is a poorly absorbed semisynthetic rifamycin derivative with a broad spectrum of antibacterial activity including gram-positive and gram-negative bacteria, both aerobes and anaerobes. although originally developed for the treatment of infectious diarrhea, the appreciation of the pathogenic role of gut bacteria in several organic and functional gastrointestinal diseases has increasingly broadened its clinical use. the availability of a topical formulation (a cream containing 5% of the d ...	2005	15855757
the cytolethal distending toxin of haemophilus ducreyi aggravates dermal lesions in a rabbit model of chancroid.	haemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, produces a cytolethal distending toxin (hdcdt) that inhibits cultured cell proliferation, leading to cell death. a rabbit model of dermal infection was used to investigate the roles of h. ducreyi bacteria and hdcdt in the development, clinical appearance, and persistence of infection. a non-toxin producing h. ducreyi strain, and for comparison purposes a non-capsulated haemophilus influenzae strain, were inoc ...	2005	15876546
killing of dsra mutants of haemophilus ducreyi by normal human serum occurs via the classical complement pathway and is initiated by immunoglobulin m binding.	previously, we showed that serum resistance in haemophilus ducreyi type strain 35000hp required expression of the outer membrane protein dsra because the isogenic dsra mutant fx517 is highly serum susceptible. in this study, we confirmed this finding by construction of additional serum-susceptible dsra mutants in more recently isolated serum-resistant strains. we also demonstrated that killing of dsra mutants required an intact classical complement cascade but not the alternative or mannan-bindi ...	2005	15908371
attenuated salmonella typhimurium sl3261 as a vaccine vector for recombinant antigen in rabbits.	oral live salmonella vaccine vectors expressing recombinant guest antigens help stimulate systemic, mucosal, humoral, and cell-mediated immune responses against salmonella and recombinant antigens. it may be possible to use them effectively against haemophilus ducreyi, the bacterium that causes chancroid, a sexually transmitted genital ulcer disease. this study aimed to test the feasibility of using oral salmonella vaccine vectors for the evaluation of chancroid vaccine candidates in the tempera ...	2005	15914198
treatment of chancroid in resource-poor countries.	chancroid, formerly a major cause of the genital ulcer disease syndrome, remains an important cofactor in both the transmission and acquisition of hiv-1 infection. those countries with the greatest burden of hiv also have some of the highest prevalence rates of chancroid worldwide. the diagnosis of chancroid, caused by the fastidious bacterium haemophilus ducreyi, is both expensive and difficult in many resource-poor areas. these areas of the world use syndromic management to treat genital ulcer ...	2005	15918786
cellular internalization of cytolethal distending toxin: a new end to a known pathway.	the cytolethal distending toxins (cdts) are unique in their ability to induce dna damage, activate checkpoint responses and cause cell cycle arrest or apoptosis in intoxicated cells. however, little is known about their cellular internalization pathway. we demonstrate that binding of the haemophilus ducreyi cdt (hdcdt) on the plasma membrane of sensitive cells was abolished by cholesterol extraction with methyl-beta-cyclodextrin. the toxin was internalized via the golgi complex, and retrogradely ...	2005	15953025
sialylation of group b streptococcal capsular polysaccharide is mediated by cpsk and is required for optimal capsule polymerization and expression.	several bacterial pathogens have evolved the means to escape immune detection by mimicking host cell surface carbohydrates that are crucial for self/non-self recognition. sialic acid, a terminal residue on these carbohydrates, inhibits activation of the alternate pathway of complement by recruiting the immune modulating molecule factors h, i, and ic3b. sialylation of capsular polysaccharide (cps) is important for virulence of group b streptococci (gbs), a significant human pathogen. we previousl ...	2005	15968073
trafficking pathways and characterization of cd4 and cd8 cells recruited to the skin of humans experimentally infected with haemophilus ducreyi.	t-cell homing to infected skin is not well studied in humans. we examined sites experimentally infected with haemophilus ducreyi by immunohistochemistry and flow cytometry for expression of receptors and ligands involved in cutaneous t-cell homing and determined the phenotypes of the t cells that trafficked to skin. endothelial cells expressed e-selectin in infected but not uninfected skin, while peripheral node addressin (pnad) was minimally expressed in all samples. cc chemokine ligand 27 (ccl ...	2005	15972475
[rapid diagnosis of outbreak-prone bacterial diseases].		2005	15978360
in vitro and in vivo activity of combination antimicrobial agents on haemophilus ducreyi.	development of single dose antibiotic treatments for chancroid has been followed by drug-resistant haemophilus ducreyi in endemic areas. we examined the activity and interactions of antimicrobial agents and combinations against h. ducreyi.	2005	16046468
the family of serratia type pore forming toxins.	the serratia marcescens hemolysin represents the prototype of a growing family of pore forming toxins. the available bacterial genome sequences reveal serratia hemolysin homologues in additional species. however, only s. marcescens hemolysin has been studied in great molecular detail. this family of toxins has nothing in common with the pore forming toxins of e. coli type (rtx toxins), the staphylococcus aureus alpha-toxin or the thiol activated toxin of group a beta-hemolytic streptococci (stre ...	2005	16101433
characterization of genetic and phenotypic diversity of invasive nontypeable haemophilus influenzae.	the ability of unencapsulated (nontypeable) haemophilus influenzae (nthi) to cause systemic disease in healthy children has been recognized only in the past decade. to determine the extent of similarity among invasive nontypeable isolates, we compared strain r2866 with 16 additional nthi isolates from blood and spinal fluid, 17 nasopharyngeal or throat isolates from healthy children, and 19 isolates from middle ear aspirates. the strains were evaluated for the presence of several genetic loci th ...	2005	16113304
identification of a novel sialic acid transporter in haemophilus ducreyi.	haemophilus ducreyi, the causative agent of chancroid, produces a lipooligosaccharide (los) which terminates in n-acetyllactosamine. this glycoform can be further extended by the addition of a single sialic acid residue to the terminal galactose moiety. h. ducreyi does not synthesize sialic acid, which must be acquired from the host during infection or from the culture medium when the bacteria are grown in vitro. however, h. ducreyi does not have genes that are highly homologous to the genes enc ...	2005	16177350
x-ray absorption investigation of a unique protein domain able to bind both copper(i) and copper(ii) at adjacent sites of the n-terminus of haemophilus ducreyi cu,zn superoxide dismutase.	the n-terminal metal binding extension of the cu,zn superoxide dismutase from haemophilus ducreyi is constituted by a histidine-rich region followed by a methione-rich sequence which shows high similarity with protein motifs involved in the binding of cu(i). x-ray absorption spectroscopy experiments selectively carried out with peptides corresponding to the two metal binding regions indicate that both sequences can bind either cu(ii) or cu(i). however, competition experiments demonstrate that cu ...	2005	16185082
franksum: new feature selection method for protein function prediction.	in the study of in silico functional genomics, improving the performance of protein function prediction is the ultimate goal for identifying proteins associated with defined cellular functions. the classical prediction approach is to employ pairwise sequence alignments. however this method often faces difficulties when no statistically significant homologous sequences are identified. an alternative way is to predict protein function from sequence-derived features using machine learning. in this ...	2005	16187402