Syphilis is a global, re-emerging sexually transmitted infection and congenital syphilis remains a major cause of adverse pregnancy outcomes due to bacterial infection in developing nations with a high rate of fetus loss. The molecular mechanisms involved in pathogenesis of the causative agent, subsp. remain poorly understood due to the difficulties of working with this pathogen, including the inability to grow it in pure culture. To reduce the spread of syphilis, we must first increase our knowledge of the virulence factors of and their contribution to syphilis manifestations. Tp0954 was predicted to be a surface lipoprotein of . Therefore, we experimentally demonstrated that Tp0954 is indeed a surface protein and further investigated its role in mediating bacterial attachment to various mammalian host cells. We found that expression of Tp0954 in a poorly adherent, but physiologically related derivative strain of the Lyme disease causing spirochete B314 strain promotes its binding to epithelial as well as non-epithelial cells including glioma and placental cell lines. We also found that Tp0954 expression facilitates binding of this strain to purified dermatan sulfate and heparin, and also that bacterial binding to mammalian cell lines is mediated by the presence of heparan sulfate and dermatan sulfate in the extracellular matrix of the specific cell lines. These results suggest that Tp0954 may be involved not only in initiating infection by colonizing skin epithelium, but it may also contribute to disseminated infection and colonization of distal tissues. Significantly, we found that Tp0954 promotes binding to the human placental choriocarcinoma BeWo cell line, which is of trophoblastic endocrine cell type, as well as human placental tissue sections, suggesting its role in placental colonization and possible contribution to transplacental transmission of . Altogether, these novel findings offer an important step toward unraveling syphilis pathogenesis, including placental colonization and vertical transmission from mother to fetus during pregnancy.
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http://dx.doi.org/10.3389/fmicb.2020.621654 | DOI Listing |
Food Chem
January 2025
Department of Nanotechnology, North-Eastern Hill University (NEHU), Shillong 793022, Meghalaya, India. Electronic address:
In this study, an alginate-chitosan (AL-CS) nanocomplex decorated with vitamin C coated iron oxide nanoparticles (FeO-vit C NPs) was investigated as a novel nanoiron fortification agent. The FeO-vit C NPs decorated on AL-CS nanocomplex underwent comprehensive characterization, including zeta potential, fourier transform infrared spectroscopy, X-ray diffraction, and UV-vis spectroscopy. The transmission electron microscopy (TEM) analysis confirmed the decoration of FeO-vit C NPs on AL-CS nanocomplex.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. Electronic address:
Tumor cells must optimize metabolite acquisition between synthesis and uptake from a microenvironment characterized by hypoxia, lactate accumulation, and depletion of many amino acids, including arginine. We performed a metabolism-focused functional screen using CRISPR-Cas9 to identify pathways and factors that enable tumor growth in an arginine-depleted environment. Our screen identified the SLC-family transporter SLC7A5 as required for growth, and we hypothesized that this protein functions as a high-affinity citrulline transporter.
View Article and Find Full Text PDFFEBS J
January 2025
Department of Drug Design and Pharmacology, University of Copenhagen, Denmark.
The glucagon-like peptide-1 receptor (GLP-1R) plays an important role in regulating insulin secretion and reducing body weight, making it a prominent target in the treatment of type 2 diabetes and obesity. Extensive research on GLP-1R signaling has provided insights into the connection between receptor function and physiological outcomes, such as the correlation between Gs signaling and insulin secretion, yet the exact mechanisms regulating signaling remain unclear. Here, we explore the internalization pathway of GLP-1R, which is crucial for controlling insulin release and maintaining pancreatic beta-cell function.
View Article and Find Full Text PDFEur J Epidemiol
January 2025
Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden.
The Stockholm Early Detection of Cancer Study (STEADY-CAN) cohort was established to investigate strategies for early cancer detection in a population-based context within Stockholm County, the capital region of Sweden. Utilising real-world data to explore cancer-related healthcare patterns and outcomes, the cohort links extensive clinical and laboratory data from both inpatient and outpatient care in the region. The dataset includes demographic information, detailed diagnostic codes, laboratory results, prescribed medications, and healthcare utilisation data.
View Article and Find Full Text PDFNPJ Precis Oncol
January 2025
Zentalis Pharmaceuticals, Inc., San Diego, CA, USA.
Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.
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