ABSTRACT The influence of the skin microbiota on host susceptibility to infectious agents is largely unexplored. harbors diverse bacterial species that may promote or antagonize growth an invading pathogen. We developed a human infection model for Haemophilus ducreyi in which volunteers are inoculated upper arm. After inoculation, papules form and either spontaneously resolve progress pustules. To examine role outcome H. infection, we analyzed microbiomes four dose-matched pairs “resolvers”...

The lipooligosaccharides (LOS) of strains Haemophilus ducreyi, Neisseria gonorrhoeae, meningitidis, and lactamica contain epitopes that are antigenically structurally similar to carbohydrates present in human glycosphingolipids. LOS from influenzae H. biogroup aegyptius were tested for the binding monoclonal antibodies (MAbs) bind glycosphingolipids possessing Gal beta 1-4GlcNAc (MAb 3F11) alpha 1-4Gal 1-4Glc anti-Pk). In solid-phase radioimmunoassays, 18 19 type b (Hib), 8 nontypeable...

Journal Article Experimental Human Infection with Haemophilus ducreyi Get access Stanley M. Spinola, Spinola Reprints or correspondence: Dr. Dept. of Medicine, 435 Emerson Hall, 545 Barnhill Dr., Indianapolis, IN 46202. Search for other works by this author on: Oxford Academic PubMed Google Scholar Linda Wild, Wild Michael A. Apicella, Apicella Anthony Gaspari, Gaspari Campagnari The Infectious Diseases, Volume 169, Issue 5, May 1994, Pages 1146–1150,...

Human subjects were experimentally infected with Haemophilus ducreyi for up to 2 weeks. Bacterial suspensions delivered into the epidermis and dermis through puncture wounds made by an allergy-testing device. Subjects developed papular lesions that evolved pustules resembling natural disease. Some resolved spontaneously, indicating host responses may clear infection. Bacteria shed intermittently from lesions, suggesting H. be transmissible before ulceration. Host infection consisted...

Human volunteers were challenged with Haemophilus ducreyi. Twenty subjects inoculated 2 doses (approximately 30 cfu) of live and 1 dose heat-killed bacteria at 3 sites on the arm. Eight assigned to biopsy or 4 days after inoculation, 12 biopsied they developed a painful pustular lesion followed until disease resolved. Papules 95% 40 infected (95% confidence interval [CI], 83. 1%-99.4%). In 24 end point, 27% papules resolved, 69% CI, 47.1%-86.6%) evolved into pustules, 4% remained papular...

The mouse and rabbit intradermal injection models have been used to define factors that may be important in Haemophilus ducreyi pathogenesis. We H. strains with diverse geographic origins phenotypic characteristics evaluate the experimental models. Injection of live heat-killed bacteria caused skin abscesses both Semiquantitative cultures injected showed failed replicate animal tissue. These data suggested lesions were by a heat-stable substance such as lipooligosaccharide (LOS). In mice,...

Journal Article Epidemiology of Colonization by Nontypable Haemophilus influenzae in Children: A Longitudinal Study Get access Stanley M. Spinola, Spinola From the Departments Pediatrics, Medicine, and Microbiology Immunology, University North Carolina School Chapel Hill, Search for other works this author on: Oxford Academic PubMed Google Scholar James Peacock, Peacock Floyd W. Denny, Denny Dana L. Smith, Smith Janne G. Cannon Please address requests reprints to Dr. Cannon, Department...

Haemophilus ducreyi causes chancroid, which facilitates transmission of human immunodeficiency virus type 1. To better understand the biology H. ducreyi, we developed a inoculation model. In present article, describe clinical outcomes for 267 volunteers who were infected with ducreyi. There was relationship between papule formation and estimated delivered dose. The outcome (either pustule or resolution) sites given subject not independent; most important determinants sex host effects. When...

In a previous study, Haemophilus ducreyi was found in the pustule and dermis of samples obtained at clinical end point human model infection. To understand kinetics localization, we examined infected sites 0, 24, 48 h after inoculation point. Immediately inoculation, bacteria were predominantly but also epidermis. Few detectable 24 h; however, by h, readily seen dermis. H. associated with polymorphonuclear leukocytes macrophages its base, not T cells, Langerhans' or fibroblasts. colocalized...

ABSTRACT The immune response to Haemophilus ducreyi is mediated in part by T cells infiltrating the site of infection. In this study, we show that H. antigen preparations inhibited proliferation peripheral blood mononuclear and primary human T-cell lines. also Jurkat induced apoptosis cells, confirmed through detection DNA degradation membrane unpacking. cytotoxic product(s) was present cell-free culture supernatant whole-cell heat labile. produces two known heat-labile toxins, a hemolysin...

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-inactivatedmutant (FX504) on their upper arms double-blinded, escalating dose-response study. Papules developed at similar rates sites inoculated mutant or parent. The pustule-formation rate was 55% (95% confidence interval [CI], 30.8%–78.5%) parent 0 CI, 0–10.5%) (P < .0001). recovery H. from...

Haemophilus ducreyi expresses a peptidoglycan-associated lipoprotein (PAL) that exhibits extensive homology to influenzae protein 6. We constructed an isogenic PAL mutant (35000HP-SMS4) by the use of suicide vector contains lacZ as counterselectable marker. H. 35000HP-SMS4 and its parent, 35000HP, had similar growth rates in broth lipooligosaccharide profiles. formed smaller, more transparent colonies than 35000HP and, unlike was hypersensitive antibiotics. Complementation trans restored...

Haemophilus ducreyi must adapt to the environment of human host establish and maintain infection in skin. Bacteria generally utilize stress response systems, such as CpxRA two-component system, hostile environments. is only obvious system contained H. genome negatively regulates lspB-lspA2 operon, which encodes proteins that enable organism resist phagocytosis. We constructed an unmarked, in-frame cpxA deletion mutant, 35000HPDeltacpxA. In inoculation experiments, 35000HPDeltacpxA formed...

ABSTRACT To adapt to stresses encountered in stationary phase, Gram-negative bacteria utilize the alternative sigma factor RpoS. However, some species lack RpoS; thus, it is unclear how stationary-phase adaptation regulated these organisms. Here we defined growth-phase-dependent transcriptomes of Haemophilus ducreyi , which lacks an RpoS homolog. Compared mid-log-phase organisms, cells harvested from phase upregulated genes encoding several virulence determinants and a homolog hfq ....

During microbial infection, macrophages are polarized to classically activated (M1) or alternatively (M2) cells in response components and host immune mediators. Proper polarization of is critical for bacterial clearance. To study the role macrophage during Haemophilus ducreyi we analyzed a panel surface markers skin biopsy specimens pustules obtained from experimentally infected volunteers. Lesional expressed characteristic both M1 M2 polarization. Monocyte-derived (MDM) also mixed profile...

ABSTRACT Neisseria gonorrhoeae is a leading cause of sexually transmitted infection (STI) and priority AMR pathogen. Two narrow host range plasmids, p bla pConj, have contributed to ending penicillin tetracycline therapy, respectively, undermine current prevention strategies including Doxy-PEP. Here, we investigated the origin evolution beta-lactamase plasmid, . We show that interplay between pConj influences their co-occurrence spread in gonococcal population. demonstrate was acquired by...

Antigen processing and presentation via major histocompatibility complex (MHC) molecules are central to immune surveillance. Yet, quantifying the dynamic activity of MHC class I II antigen remains a critical challenge, particularly in diseases like cancer, infection autoimmunity where these pathways often disrupted. Current methods fall short providing precise, sample-specific insights into presentation, limiting our understanding evasion therapeutic responses. Here, we present PSAA...

ABSTRACT Haemophilus ducreyi causes the genital ulcer disease chancroid and cutaneous ulcers in children. To study its pathogenesis, we developed a human challenge model which infect skin on upper arm of volunteers with H. to pustular stage disease. The has been used define lesional architecture, describe immune infiltrate into infected sites using flow cytometry, explore molecular basis response bulk RNA-seq. Here, single cell RNA-seq (scRNA-seq) spatial transcriptomics simultaneously...

ABSTRACT Haemophilus ducreyi causes cutaneous ulcers in children who live yaws-endemic countries and the genital ulcer disease chancroid. In human host, H. resides an abscess may need to resist both heat oxidative stress, which result aggregation misfolding of bacterial proteins. Escherichia coli , hslUV ( clpYQ ) operon encodes a proteasome-like complex that degrades misfolded proteins is upregulated during shock. previous studies, we showed transcripts are experimental lesions caused by...

Haemophilus ducreyi synthesizes fine, tangled pili composed predominantly of a protein whose apparent molecular weight is 24,000 (24K). A hybridoma, 2D8, produced monoclonal antibody (MAb) that bound to 24K in H. strains isolated from diverse geographic locations. lambda gt11 library was screened with MAb 2D8. 3.5-kb chromosomal insert one reactive plaque amplified and ligated into the pCRII vector. The recombinant plasmid, designated pHD24, expressed Escherichia coli INV alpha F coding...

An intact Haemophilus ducreyi flp operon is essential for microcolony formation in vitro. tadA the 9th of 15 genes and has homology to NTPases type IV secretion systems. Fifteen human volunteers were experimentally infected with both H. 35000HP mutant, 35000HP.400. Papules developed at similar rates sites inoculated mutant parent, while pustules formed 36.4% parent 0% (P = 0.001). Compared 35000HP, 35000HP.400 had only a modest but significant reduction lesion scores temperature-dependent...