| 1. |
- Hollandsworth, Hannah M., et al.
(författare)
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Fluorophore-conjugated Helicobacter pylori recombinant membrane protein (HopQ) labels primary colon cancer and metastases in orthotopic mouse models by binding CEA-related cell adhesion molecules
- 2020
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Ingår i: Translational Oncology. - : Elsevier. - 1944-7124 .- 1936-5233. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- HopQ is an outer-membrane protein of Helicobacter pylori that binds to human carcinoembryonic antigen-related cell-adhesion molecules (CEACAMs) with high specificity. We aimed to investigate fluorescence targeting of CEACAM-expressing colorectal tumors in patient-derived orthotopic xenograft (PDOX) models with fluorescently labeled recombinant HopQ (rHopQ). Western blotting, flow cytometry and ELISA were performed to determine the efficiency of rHopQ binding to CEACAMs. rHopQ was conjugated to IR800DyeCW (rHopQ-IR800). Nude mice received orthotopic implantation of colon cancer tumors. Three weeks later, mice were administered 25 μg or 50 μg HopQ-IR800 and imaged 24 or 48 h later. Intravital images were analyzed for tumor-to-background ratio (TBR). Flow cytometry and ELISA demonstrated binding of HopQ to CEACAM1, 3 and 5. Dose-response intravital imaging in PDOX models demonstrated optimal results 48 h after administration of 50 μg rHopQ-IR800 (TBR = 3.576) in our protocol. Orthotopic models demonstrated clear tumor margins of primary tumors and small regional metastases with a mean TBR = 3.678 (SD ± 1.027). rHopQ showed specific binding to various CEACAMs in PDOX models. rHopQ may be useful for CEACAM-positive tumor and metastasis detection for pre-surgical diagnosis, intra-operative imaging and fluorescence-guided surgery.
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| 2. |
- Catton, Erin A., et al.
(författare)
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Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Life-threatening bacterial infections in women after childbirth, known as puerperal sepsis, resulted in classical epidemics and remain a global health problem. While outbreaks of puerperal sepsis have been ascribed to Streptococcus pyogenes, little is known about disease mechanisms. Here, we show that the bacterial R28 protein, which is epidemiologically associated with outbreaks of puerperal sepsis, specifically targets the human receptor CEACAM1. This interaction triggers events that would favor the development of puerperal sepsis, including adhesion to cervical cells, suppression of epithelial wound repair and subversion of innate immune responses. High-resolution structural analysis showed that an R28 domain with IgI3-like fold binds to the N-terminal domain of CEACAM1. Together, these findings demonstrate that a single adhesin-receptor interaction can drive the pathogenesis of bacterial sepsis and provide molecular insights into the pathogenesis of one of the most important infectious diseases in medical history.
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| 3. |
- Sikora, K., et al.
(författare)
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Heavy metals effect on the rat uterus and effectiveness of vitamin E treatment
- 2023
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Ingår i: Jordan Journal of Biological Sciences. - : Hashemite University. - 1995-6673. ; 16:3, s. 455-465
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Tidskriftsartikel (refereegranskat)abstract
- Environmental pollution by heavy metals (HMs) is an increasingly critical problem that is posing a growing threat to reproductive health. Consequently, the aim of the current research was to study changes in rat uterus under 90 days of HMs exposure and estimate the efficacy and benefits of vitamin E treatment. Female rats were randomly divided into three groups: untreated animals (control group); animals orally treated with the HMs mixture (HM group); and animals treated simultaneously with HMs and vitamin E (HM+E group). The toxic effects of the HMs (comprising Zn, Cu, Mn, Fe, Pb, and Cr) on the uterus of rats were investigated by histological, morphometrical, spectrophotometrical, and statistical methods.Long-term HMs exposure triggered pathological (degenerative, inflammation, and atrophic) changes in the rat uterus together with a significant reduction of the uterine-wall thickness (37.99%, p<0.0001) compared to the control. In contrast, there was a lower intensity of morphological lesions and wall thickness decrease (26.03%, p<0.0001) in the uterus, in rats that underwent treatment with vitamin E. A substantial bioaccumulation of zinc, copper, manganese, iron, lead, and chromium general levels in the rat uterus was demonstrated in both the HM group (74.46%, p<0.0001) and the HM+E group (49.81%, p<0.0001), as compared to the control group. The lowest accumulative potential belonged to Zn and the highest to Pb. The results obtained showed a significant decline in the weight of animals treated by HMs in both HM (18,21%, p<0.01) and HM+E (13,09%; p<0.05) groups compared to the control. Our findings have demonstrated that treatment with vitamin E in HM-induced intoxication has a significant restrain of HMs accumulation (up to 16.46%, p<0.0001) together with morphometric variations (less on 16.17%, p<0.01).In summary, long-term exposure to the HMs mixture had a pernicious toxic effect on the morphology and chemical content of the uterus of rats (strong negative correlations). Treatment with vitamin E significantly reversed the HMs impact on the uterus but did not demonstrate absolute protection.
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| 4. |
- van Sorge, Nina M., et al.
(författare)
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Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors
- 2021
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Ingår i: EMBO Journal. - : Wiley-VCH Verlagsgesellschaft. - 0261-4189 .- 1460-2075. ; 40
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus agalactiae, also known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria to epithelial surfaces. GBS adhesins have been identified to bind extracellular matrix components and cellular receptors. However, several putative adhesins have no host binding partner characterised. We report here that surface-expressed β protein of GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that an IgSF domain in β represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessment revealed that this newly identified IgI3 fold is not exclusively present in GBS but is predicted to be present in adhesins from other clinically important human pathogens. In agreement with this prediction, we found that CEACAM1 binds to an IgI3 domain found in an adhesin from a different streptococcal species. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.
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