the role of haemophilus ducreyi bacteria, cytotoxin, endotoxin and antibodies in animal models for study of chancroid.haemophilus ducreyi cytotoxin-positive and -negative strains as well as bacterial sonicates and lipooligosaccharides (los) from such strains were evaluated for the capacity to produce dermonecrotic lesions, especially ulcers, after intradermal injections to rabbits and to different mouse strains, including nude mice. dermonecrotic lesions of the ulcerous type were observed within 4 days and they were developed in both rabbits and mice with about 10(7) colony forming units (cfu) of h. ducreyi. vi ...19921291843
lipooligosaccharides (los) of some haemophilus species mimic human glycosphingolipids, and some los are sialylated.the lipooligosaccharides (los) of strains of haemophilus ducreyi, neisseria gonorrhoeae, neisseria meningitidis, and neisseria lactamica contain epitopes that are antigenically and structurally similar to carbohydrates present in human glycosphingolipids. los from strains of haemophilus influenzae and h. influenzae biogroup aegyptius were tested for the binding of monoclonal antibodies (mabs) that bind to human glycosphingolipids possessing gal beta 1-4glcnac (mab 3f11) and gal alpha 1-4gal beta ...19921372291
pathophysiological concept of haemophilus ducreyi infection (chancroid)our knowledge concerning the pathogenesis of infection due to haemophilus ducreyi is incomplete. in order to produce disease, h. ducreyi must presumably penetrate the skin of the external genitalia, colonize subcutaneous tissues, then produce tissue damage which results in ulcer formation. penetration of the normal skin most likely occurs via minor abrasions. adherence of h. ducreyi to different cell lines in vitro has been described, and might be mediated by adhesions such as pili or haemagglut ...19921391058
evaluation of new anti-infective drugs for the treatment of chancroid. infectious diseases society of america and the food and drug administration.chancroid is a mucocutaneous infection caused by haemophilus ducreyi that produces ulcerative lesions and enhances the efficiency of transmission of human immunodeficiency virus (hiv). confirmation of infection by culture of h. ducreyi is essential in therapeutic trials. minimal inhibitory concentrations of antibiotics for the isolate should be determined by agar dilution. patients should be evaluated by appropriate laboratory tests for syphilis, infection with herpes simplex virus, gonorrhea, a ...19921477217
hiv and other sexually transmitted diseases among female prostitutes in 1988, 1233 prostitutes from different geographic areas of kinshasa participated in a cross-sectional survey on hiv infection and other sexually transmitted diseases (stds). despite relatively good knowledge about aids and stds, the reported preventive behaviour was poor. only 12% of the women reported regular use of condoms, while greater than 50% of the women reported regular use of antibiotics and 38% reported doing nothing specific to prevent stds. thirty-five per cent of the women were hi ...19911883543
treatment of chancroid, 1989.since recommendations for the treatment of chancroid were made in 1985, in vitro and in vivo data indicate that the two drugs recommended, erythromycin (500 mg four times a day for 7 days) and ceftriaxone (250 mg intramuscularly in a single dose), remain effective. the alternative therapies of trimethoprim-sulfamethoxazole (160/800 mg twice a day for 7 days) and amoxicillin-clavulanic acid (500/125 mg three times a day for 7 days) also appear to be effective, although there has been little exper ...19902201074
the epidemiology of sexually transmitted diseases in africa and latin america.we review some aspects of the epidemiology of sexually transmitted diseases (stds) in the developing countries of africa and latin america. apart from their elevated prevalence, they are responsible for important morbidity in mother and child. stillbirth, premature delivery, conjunctivitis, and respiratory tract morbidity of the neonate are frequently caused by stds. sequelae in adult women include pelvic inflammatory disease, ectopic pregnancy, and infertility. the emergence of antimicrobial re ...19902202406
chancroid and the role of genital ulcer disease in the spread of human retroviruses.chancroid is the most prevalent form of genital ulcer disease in developing countries and is undergoing a resurgence in industrialized countries. as a result of a nonspecificity of the clinical findings, the etiologic diagnosis of genital ulcer disease requires laboratory support. genital ulcer disease is a risk factor for the transmission of human retroviral infections. an understanding of this interaction is emerging and will impact on the treatment and control programs for the agents causing ...19902246947
etiology of nonvesicular genital ulcers in winnipeg.twenty-eight patients with recent onset of nonvesicular ulcerative genital lesions were studied prospectively to define the microbial etiology. causative agents identified included herpes simplex virus (hsv), chlamydia trachomatis, haemophilus ducreyi, and treponema pallidum. three women and 25 men (seven of whom were homosexual) were studied. ten patients did not have an etiology identified. nine patients had syphilis, six had genital herpes, one had chancroid, one had granuloma inguinale, and ...19873494322
virulence factors of haemophilus ducreyi.we investigated the susceptibility of virulent and avirulent strains of haemophilus ducreyi to the bactericidal activity of normal human serum and to phagocytosis and killing by human polymorphonuclear leukocytes (pmnl). strains were defined as virulent if intradermal inoculation into a rabbit produced a typical necrotic lesion. nonvirulent strains produced no cutaneous lesions in rabbits. virulent strains were resistant to the complement-mediated lethal action of normal human and rabbit sera, w ...19846607219
bacterial [cu,zn]-superoxide dismutase: phylogenetically distinct from the eukaryotic enzyme, and not so rare after all!copper- and zinc-containing superoxide dismutases ([cu,zn]-sods) are generally considered almost exclusively eukaryotic enzymes, protecting the cytosol and extracellular compartments of higher organisms from damage by oxygen free-radicals. the recent description of a few examples of bacterial forms of the enzyme, located in the periplasm of different gram-negative micro-organisms, prompted a re-evaluation of this general perception. a pcr-based approach has been developed and used successfully t ...19957496539
swine model of haemophilus ducreyi infection.haemophilus ducreyi is a strict human pathogen that causes sexually transmitted genital ulcer disease. we infected domestic swine with h. ducreyi 35000, resulting in the development of cutaneous ulcers histologically resembling human chancroid lesions. intraepidermal lesions progressed from pustules to ulcers containing polymorphonuclear leukocytes and were accompanied by a dermal inflammatory infiltrate containing t cells and macrophages. h. ducreyi was recovered from lesions up to 17 days afte ...19957622236
serum bactericidal activity and phagocytosis in host defence against haemophilus ducreyi.serum bactericidal activity and phagocytic killing are two important mechanisms involved in the host defence against bacteria. using some in vitro methods, serum bactericidal assay, phagocytic killing by polymorphonuclear leukocytes (pmn) and chemiluminescence, we have evaluated the significance of these mechanisms in the killing of haemophilus ducreyi bacteria. furthermore, induction of c3 conversion and deposition of immunoglobulins, c1q and c3, on the surface of bacteria was studied by crosse ...19957783597
single dose azithromycin for the treatment of chancroid: a randomized comparison with erythromycin.chancroid is endemic in sub-saharan africa and enhances the sexual transmission of the human immunodeficiency virus type 1 (hiv-1). azithromycin is an orally absorbed macrolide antibiotic that is active against haemophilus ducreyi, the causative agent of chancroid, and has pharmacokinetic properties that are suitable for single dosing.19947974076
experimental human infection with haemophilus ducreyi.four subjects were experimentally infected with haemophilus ducreyi. lesions developed only at sites where live bacteria were inoculated on abraded skin. no subject developed fever, lymphadenopathy, or disseminated infection during a 3-day observation period. two subjects who were rechallenged 2 months after initial infection also developed lesions. the amount of h. ducreyi recovered from 10 of 12 biopsies that were semiquantitatively cultured varied widely. similar histologic features were pres ...19948169411
antibodies directed against haemophilus ducreyi heat shock proteins.the response to heat shock in haemophilus ducreyi has been investigated by labelling newly synthesized proteins with a pulse of 35s-methionine at a range of temperatures between 30-40 degrees c. proteins were then separated by sds-page and analysed by autoradiography of the resultant profiles. four heat shock proteins (hsp) were identified of apparent molecular weight < 14, 58.5, 74 and 78 kda. the three larger proteins appeared to be independently controlled and inducible in a range of h. ducre ...19938255206
antigen detection and immunological typing of haemophilus ducreyi with a specific rabbit polyclonal serum.a rabbit polyclonal serum was raised against the 29-kda species-specific marker, as well as the 30- to 34-kda immunotype-specific markers of haemophilus ducreyi described elsewhere (e. roggen, s. de breucker, e. van dyck, and p. piot, infect. immun. 60:590-595, 1992). these antigens were purified from a cocktail of h. ducreyi isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. the immune serum reacted in enzyme-linked immunosorbent assay (elisa) preferentially with h. ducreyi, ...19938349759
simultaneous pcr detection of haemophilus ducreyi, treponema pallidum, and herpes simplex virus types 1 and 2 from genital ulcers.a multiplex pcr (m-pcr) assay with colorimetric detection was devised for the simultaneous amplification of dna targets from haemophilus ducreyi, treponema pallidum, and herpes simplex virus (hsv) types 1 and 2. by using target-specific oligonucleotides in a microwell format, 298 genital ulcer swab specimens collected in new orleans during three intervals from 1992 through 1994 were evaluated. the results of the m-pcr assay were compared with the results of dark-field microscopy and h. ducreyi c ...19968748271
[sexually transmitted diseases in men].sexually transmitted diseases (std) constitute a frequent presenting complaint. the epidemiology of human immunodeficiency virus (hiv) infection is identical to that of std and must therefore be systematically investigated in the presence of any std. chlamydia trachomatis (ct) is involved in the majority of cases of urethritis and epididymitis in young subjects and is present in the urethra of 10% of subjects with a genital ulcer. genital ulcers are due to either treponema pallidum, haemophilus ...19968763705
increased risk of infection with human immunodeficiency virus type 1 among uncircumcised men presenting with genital ulcer disease in kenya.the factors responsible for the explosive spread of human immunodeficiency virus type 1 (hiv-1) in sub-saharan africa continue to be identified and debated. one of the most controversial factors has been male circumcision. this cross-sectional study was conducted to measure the association between circumcision status and infection with hiv-1 among men with genital ulcer disease. eight hundred and ten men participated in the study, of whom 190 (23%) were hiv-1-positive. a logistic regression mode ...19968879763
characterization of a transposon tn916-generated mutant of haemophilus ducreyi 35000 defective in lipooligosaccharide define the role of the surface lipooligosaccharide (los) of haemophilus ducreyi in the pathogenesis of chancroid, tn916 mutants of h. ducreyi 35000 defective in expression of the murine monoclonal antibody (mab) 3f11 epitope on h. ducreyi los were identified by immunologic screening. one mutant, designated 1381, has an los which lacks the mab 3f11 epitope and migrates with an increased mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. the gene disrupted by the tn916 eleme ...19979260947
the association of herpes simplex virus type 2 (hsv-2), haemophilus ducreyi, and syphilis with hiv infection in young men in northern evaluate the association between sexually transmitted diseases that commonly may cause genital ulceration and prevalent and incident hiv infections, we conducted three case control studies in a cohort of 21-year-old male military conscripts in northern thailand. the men were evaluated at baseline in 1991 and semiannually until their discharge 2 years later. serologic evidence of infection with herpes simplex virus type 2 (hsv-2), haemophilus ducreyi, and hiv were more frequent at baseline in ...19979402077
groel heat shock protein of haemophilus ducreyi: association with cell surface and capacity to bind to eukaryotic cells.the haemophilus ducreyi homolog of groel, a 58.5-kda heat shock protein (hsp), is a dominant protein produced not only in response to heat stress but also under in vitro growth conditions. extracellular localization of the 58.5-kda hsp was investigated by whole-cell enzyme-linked immunosorbent assay (elisa) and immunoelectron microscopy and in supernatants of washed bacteria by immunoblotting with a haemophilus ducreyi groel-specific mouse monoclonal antibody (bb11). to investigate binding of th ...19989488422
a serosurvey of haemophilus ducreyi, syphilis, and herpes simplex virus type 2 and their association with human immunodeficiency virus among female sex workers in lagos, determine the prevalence rates of serological reactivity of haemophilus (h.) ducreyi, treponema pallidum, and herpes simplex virus type 2 (hsv-2) antibodies among female sex workers (fsws) and their association with human immunodeficiency virus (hiv) antibody status.19989587174
haemophilus ducreyi infection causes basal keratinocyte cytotoxicity and elicits a unique cytokine induction pattern in an in vitro human skin model.haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. predominantly a cutaneous pathogen, h. ducreyi is present in chancroid ulcers that are characterized by extensive neutrophil accumulation in intraepidermal lesions accompanied by a mononuclear infiltrate in the dermis. we used an in vitro human skin model composed of foreskin fibroblasts and keratinocytes to examine host skin cell interactions with h. ducreyi 35000. bacteria replicated and per ...19989596767
molecular methods for the diagnosis of genital ulcer disease in a sexually transmitted disease clinic population in northern thailand: predominance of herpes simplex virus infection.a multiplex polymerase chain reaction (m-pcr) assay that simultaneously detects the three major causes of genital ulcer disease (gud), haemophilus ducreyi, treponema pallidum, and herpes simplex virus, was used to evaluate swab specimens for 38 sequential patients with gud at a thai sexually transmitted disease clinic. subjects received clinical diagnoses and syndromic treatment. swab specimens for h. ducreyi cultures and m-pcr were obtained. no h. ducreyi cultures were positive. of 38 m-pcr spe ...19989652447
characterization of mechanisms involved in adherence of haemophilus ducreyi to eukaryotic cells.the adherence of haemophilus ducreyi to eukaryotic cells of various origins was investigated by means of a microassay using radiolabelled bacteria. the influence of physicochemical conditions and of different inhibitors on adherence to hep-2 cells and human fibroblasts was examined. h. ducreyi strains manifested substantial adherence capacity (range, 11-38% of inoculum) to different cells, not discriminating between human and animal origin. the level of adherence was temperature-dependent, being ...19989674891
standardization of the experimental model of haemophilus ducreyi infection in human subjects.human volunteers were challenged with haemophilus ducreyi. twenty subjects were inoculated with 2 doses (approximately 30 cfu) of live and 1 dose of heat-killed bacteria at 3 sites on the arm. eight subjects were assigned to biopsy 1 or 4 days after inoculation, and 12 were biopsied after they developed a painful pustular lesion or were followed until disease resolved. papules developed at 95% of 40 sites infected with live bacteria (95% confidence interval [ci], 83. 1%-99.4%). in 24 sites follo ...19989815220
etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 us cities. the genital ulcer disease surveillance determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (hiv) infection in ulcer patients in 10 us cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city. ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect haemophilus ducreyi, treponema pallidum, and herpes simplex virus (hsv); sera were tested for antibody to hiv. h. ducreyi w ...19989815237
experimental infection of human volunteers with haemophilus ducreyi does not confer protection against subsequent challenge.two groups of human volunteers were inoculated with 2 doses of live haemophilus ducreyi 35000hp. the reinfection group consisted of 7 subjects who previously had participated in experimental infection with 35000hp to the pustular stage of disease. the control group consisted of 7 naive subjects. papules developed at 92.8% (95% confidence interval [ci], 66.1%-99.8%) of sites inoculated with live bacteria, in the reinfection group, and at 85.7% (95% ci, 57.2%-98. 2%) of sites in the control group. ...199910191238
target cell range of haemophilus ducreyi hemolysin and its involvement in invasion of human epithelial cells.haemophilus ducreyi, the causative agent of chancroid, produces a hemolysin, whose role in virulence is not well defined. to assess the possible role of hemolysin in pathogenesis, we evaluated its target cell range by using wild-type h. ducreyi 35000, nonhemolytic mutants with the hemolysin structural gene deleted, and isogenic strains expressing different amounts of hemolytic activity. the cytotoxicity of the various cell types was assessed by quantitating the release of lactate dehydrogenase i ...199910417132
a randomized, double-blind, placebo-controlled trial of single-dose ciprofloxacin versus erythromycin for the treatment of chancroid in nairobi, kenya.a randomized, double-blind, placebo-controlled clinical trial was conducted in nairobi, kenya, to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid. in all, 208 men and 37 women presenting with genital ulcers clinically compatible with chancroid were enrolled. ulcer etiology was determined using culture techniques for chancroid, serology for syphilis, and a multiplex polymerase chain reaction for chancroid, syphilis, and herpes simplex virus (hs ...199910558945
human immunodeficiency virus infection and genital ulcer disease in south africa: the herpetic connection.while genital ulcers are a risk factor in hiv infection, the association of specific agents of genital ulcer disease (gud) with hiv infection may vary.200010654864
an isogenic hemoglobin receptor-deficient mutant of haemophilus ducreyi is attenuated in the human model of experimental infection.haemophilus ducreyi expresses a conserved hemoglobin-binding outer-membrane protein (hgba). to test the role of hgba in pathogenesis, we infected 9 adults with isolate 35000 and its isogenic hgba-inactivated mutant (fx504) on their upper arms in a double-blinded, escalating dose-response study. papules developed at similar rates at sites inoculated with the mutant or parent. the pustule-formation rate was 55% (95% confidence interval [ci], 30. 8%-78.5%) at parent sites and 0 (95% ci, 0-10.5%) at ...200010720530
a pilus-deficient mutant of haemophilus ducreyi is virulent in the human model of experimental infection.haemophilus ducreyi expresses fine tangled pili, which are composed predominantly of a major subunit (ftpa). confocal microscopy showed that an ftpa-specific monoclonal antibody bound to bacteria in biopsy samples obtained from infected human volunteers. to test the role of pili in pathogenesis, an isogenic mutant (35000hp-sms1) was constructed by insertionally inactivating ftpa. 35000hp-sms1 did not express ftpa and was nonpiliated but was otherwise identical to its parent, 35000hp. seven healt ...200010720550
expression of the cytolethal distending toxin (cdt) operon in actinobacillus actinomycetemcomitans: evidence that the cdtb protein is responsible for g2 arrest of the cell cycle in human t cells.we have previously shown that actinobacillus actinomycetemcomitans produces an immunosuppressive factor that is encoded by the cdtb gene, which is homologous to a family of cytolethal distending toxins (cdt) expressed by several gram-negative bacteria. in this study, we report that the cdt locus in a. actinomycetemcomitans is composed of five open reading frames, designated orf1, orf2, cdta, cdtb, and cdtc. the deduced amino acid sequences of the five open reading frames are highly conserved amo ...200010946289
expression of peptidoglycan-associated lipoprotein is required for virulence in the human model of haemophilus ducreyi infection.haemophilus ducreyi expresses a peptidoglycan-associated lipoprotein (pal) that exhibits extensive homology to haemophilus influenzae protein 6. we constructed an isogenic pal mutant (35000hp-sms4) by the use of a suicide vector that contains lacz as a counterselectable marker. h. ducreyi 35000hp-sms4 and its parent, 35000hp, had similar growth rates in broth and similar lipooligosaccharide profiles. 35000hp-sms4 formed smaller, more transparent colonies than 35000hp and, unlike its parent, was ...200011035757
effect of a cellulose acetate phthalate topical cream on vaginal transmission of simian immunodeficiency virus in rhesus monkeys.human immunodeficiency virus type 1 (hiv-1) infection continues to spread in developing countries, mostly through heterosexual transmission. the development of a safe and cost-effective topical microbicide, effective against a range of stds including hiv-1, would greatly impact the ongoing epidemic. when formulated in a vehicle, a micronized form of cellulose acetate phthalate (cap), which is an inactive pharmaceutical excipient, has been shown to inactivate hiv-1, herpes simplex virus types 1 a ...200011036053
the use of molecular techniques for the diagnosis and epidemiologic study of sexually transmitted infections.molecular diagnostic tests are more sensitive and, in many cases, more specific than conventional laboratory methods for the detection of sexually transmitted infections. here, we review recently developed molecular methods for the diagnosis and subtyping of the most common sexually transmitted infections: infections caused by chlamydia trachomatis, neisseria gonorrhoeae, human papillomavirus, trichomonas vaginalis, and the agents of genital ulcer disease (haemophilus ducreyi, herpes simplex vir ...200011095835
haemophilus ducreyi associates with phagocytes, collagen, and fibrin and remains extracellular throughout infection of human a previous study, haemophilus ducreyi was found in the pustule and dermis of samples obtained at the clinical end point in the human model of infection. to understand the kinetics of localization, we examined infected sites at 0, 24, and 48 h after inoculation and at the clinical end point. immediately after inoculation, bacteria were found predominantly in the dermis but also in the epidermis. few bacteria were detectable at 24 h; however, by 48 h, bacteria were readily seen in the pustule a ...200111254619
the impact of haemophilus ducreyi cytolethal distending toxin on cells involved in immune response.the haemophilus ducreyi cytolethal distending toxin (hdcdt) induces cell cycle arrest and thereby inhibits cell proliferation of many cultured mammalian cell-lines. we investigated the effect of hdcdt on circulating human hematopoietic cells, including t- and b-cells, monocytes and polymorphonuclear cells (pmn). lymphocytes were stimulated with t- and b-cell specific mitogens, whereas monocytes and pmn with endotoxin. hdcdt inhibited the mitogen-induced proliferation of t-cells in a dose-depende ...200111273741
haemophilus ducreyi inhibits phagocytosis by u-937 cells, a human macrophage-like cell line.haemophilus ducreyi is a gram-negative obligate human pathogen that causes the genital ulcer disease chancroid. chancroid lesions are deep necrotic ulcers with an immune cell infiltrate that includes macrophages. despite the presence of these phagocytic cells, chancroid ulcers can persist for months and live h. ducreyi can be isolated from these lesions. to analyze the interaction of h. ducreyi with macrophages, we investigated the ability of h. ducreyi strain 35000 to adhere to, invade, and sur ...200111447144
a superoxide dismutase c mutant of haemophilus ducreyi is virulent in human volunteers.haemophilus ducreyi produces a periplasmic copper-zinc superoxide dismutase (cu-zn sod), which is thought to protect the organism from exogenous reactive oxygen species generated by neutrophils during an inflammatory response. we had previously identified the gene, sodc, responsible for the production and secretion of cu-zn sod and constructed an isogenic h. ducreyi strain with a mutation in the sodc gene (35000hp-sodc-cat). compared to the parent, the mutant does not survive in the presence of ...200211854222
immunopathogenesis of haemophilus ducreyi infection (chancroid). 200211895928
etiology of genital ulcer disease and association with human immunodeficiency virus infection in two tanzanian cities.the etiological agent is usually not established in cases of genital ulcer disease (gud) in tanzania, since diagnosis and treatment of this disease are based mainly on clinical rather than microbiologic parameters. gud increases the risk of infection with hiv. however, the association between specific gud infections and hiv infection has not been fully investigated.200312567167
mutations in the lspa1 and lspa2 genes of haemophilus ducreyi affect the virulence of this pathogen in an animal model system.haemophilus ducreyi 35000hp contains two genes, lspa1 and lspa2, whose predicted protein products have molecular weights of 456,000 and 543,000, respectively (c. k. ward, s. r. lumbley, j. l. latimer, l. d. cope, and e. j. hansen, j. bacteriol. 180:6013-6022, 1998). we have constructed three h. ducreyi 35000hp mutants containing antibiotic resistance cartridges in one or both of the lspa1 and lspa2 open reading frames. western blot analysis using lspa1- and lspa2-specific monoclonal antibodies i ...200312704119
expression of the cytolethal distending toxin in a geographically diverse collection of haemophilus ducreyi clinical screen a collection of isolates of haemophilus ducreyi for expression of the cytolethal distending toxin (cdt).200312902578
molecular mimicry of host structures by lipooligosaccharides of neisseria meningitidis: characterization of sialylated and nonsialylated lacto-n-neotetraose (galbeta1-4glcnacbeta1-3galbeta1-4glc) structures in lipooligosaccharides using monoclonal antibodies and specific lectins.neisseria meningitidis lipooligosaccharides (loss) are classified into 12 immunotypes. most loss are heterogeneous in having a few components by sds-page analysis that differ antigenically and chemically. we have utilized a monoclonal antibody that recognizes lacto-n-neotetraose (lnnt) and the lectin, maackia amurensis leukoagglutinin (mal), which is specific for neunacalpha2-3galbeta1-4glcnac trisacchride sequence to characterize the 12 n. meningitidis loss. using the combination of elisa, sds- ...200114533820
differences in host susceptibility to disease progression in the human challenge model of haemophilus ducreyi infection.with human volunteers inoculated at two sites with haemophilus ducreyi, outcomes for a subject were not independent. in a reinfection trial, 2 of 11 previous pustule formers and 6 of 10 previous resolvers resolved all sites of infection. there was no correlation between serum bactericidal or phagocytic activity and outcome in the trial. these data indicate that different hosts are differentially susceptible to disease progression versus resolution in the model.200314573692
haemophilus ducreyi requires an intact flp gene cluster for virulence in intact haemophilus ducreyi flp operon is essential for microcolony formation in vitro. tada is the 9th of 15 genes in the operon and has homology to ntpases of type iv secretion systems. fifteen human volunteers were experimentally infected with both h. ducreyi 35000hp and the tada mutant, 35000hp.400. papules developed at similar rates at sites inoculated with the mutant and parent, while pustules formed at 36.4% of parent sites and at 0% of mutant sites (p = 0.001). compared to 35000hp, 350 ...200314638812
a novel lectin, dlta, is required for expression of a full serum resistance phenotype in haemophilus ducreyi.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 a ...200415155648
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 ...200515804526
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 ...200515908371
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 ...200515972475
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 ...200616426809
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 ...200616552053
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.200818227178
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 ...200919103932
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 ...200919552526
host-pathogen interplay of haemophilus ducreyi.haemophilus ducreyi, the causative agent of the sexually transmitted infection chancroid, is primarily a pathogen of human skin. during infection, h. ducreyi thrives extracellularly in a milieu of professional phagocytes and other antibacterial components of the innate and adaptive immune responses. this review summarizes our understanding of the interplay between this pathogen and its host that leads to development and persistence of disease.201019918177
deletion of mtrc in haemophilus ducreyi increases sensitivity to human antimicrobial peptides and activates the cpxra regulon.haemophilus ducreyi resists killing by antimicrobial peptides encountered during human infection, including cathelicidin ll-37, a-defensins, and ß-defensins. in this study, we examined the role of the proton motive force-dependent multiple transferable resistance (mtr) transporter in antimicrobial peptide resistance in h. ducreyi. we found a proton motive force-dependent effect on h. ducreyi's resistance to ll-37 and ß-defensin hbd-3, but not a-defensin hnp-2. deletion of the membrane fusion pro ...201121444663
haemophilus ducreyi lipooligosaccharides induce expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase via type 1 interferons and tnf-{alpha} in human dendritic cells.haemophilus ducreyi causes chancroid, a genital ulcer disease. in human inoculation experiments, most volunteers fail to clear the bacteria despite the infiltration of innate and adaptive immune cells to the infected sites. the immunosuppressive protein indoleamine 2,3-dioxygenase (ido) is a rate-limiting enzyme in the l-tryptophan-kynurenine metabolic pathway. tryptophan depletion and tryptophan metabolites contribute to pathogen persistence by inhibiting t cell proliferation, inducing t cell a ...201121576329
Expression of the Flp proteins by Haemophilus ducreyi is necessary for virulence in human volunteers.Haemophilus ducreyi, the causative agent of the sexually transmitted disease chancroid, contains a flp (fimbria like protein) operon that encodes proteins predicted to contribute to adherence and pathogenesis. H. ducreyi mutants that lack expression of Flp1 and Flp2 or TadA, which has homology to NTPases of type IV secretion systems, have decreased abilities to attach to and form microcolonies on human foreskin fibroblasts (HFF). A tadA mutant is attenuated in its ability to cause disease in hum ...201121939541
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