The response to diphtheria toxin of two sensitive cell lines, KB and HeLa, was investigated. Inhibition of the incorporation of radioactively labeled amino acids into protein was the earliest detectable effect of diphtheria toxin. It was observed that, during the period of intoxication, the cell membrane was morphologically intact and retained its semi-permeable character, although it was rendered fragile and more easily disrupted by mechanical manipulations than the normal cell. The transport of amino acids continued even after intoxicated cells had ceased to synthesize protein, and the levels accumulated were equal to those of control cells. It was observed that cultural conditions, age, and handling of cells affected their response to toxin. In early log phase cells subjected to a minimum of handling before application of the toxin, the normally observed latent period preceding detectable effects was reduced to 15 min for KB cells and 30 min for HeLa cells, shorter times than previously reported. The data are consistent with the hypothesis that diphtheria toxin enters susceptible cells, possibly by pinocytosis, and there acts upon cytoplasmic sites of protein synthesis.
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http://dx.doi.org/10.1084/jem.126.3.407 | DOI Listing |
Mem Inst Oswaldo Cruz
January 2025
Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France.
Diphtheria, a severe respiratory infection, was a major killer of children until the early years of the 20th century. Although diphtheria is now largely controlled globally thanks to vaccination, it is still endemic in some world regions and large epidemics can occur where vaccination coverage is insufficient. The pathological effects caused by its main virulence factor, diphtheria toxin, can be diminished by passive transfer of antibodies.
View Article and Find Full Text PDFBone Res
January 2025
Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong SAR, China.
Fibrotic remodeling of nucleus pulposus (NP) leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration, leading to low back pain incidence and disability. Emergence of fibroblastic cells in disc degeneration has been reported, yet their nature and origin remain elusive. In this study, we performed an integrative analysis of multiple single-cell RNA sequencing datasets to interrogate the cellular heterogeneity and fibroblast-like entities in degenerative human NP specimens.
View Article and Find Full Text PDFmBio
January 2025
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
Many bacterial toxins exert their cytotoxic effects by enzymatically inactivating one or more cytosolic targets in host cells. To reach their intracellular targets, these toxins possess functional domains or subdomains that interact with and exploit various host factors and biological processes. Despite great progress in identifying many of the key host factors involved in the uptake of toxins, significant knowledge gaps remain as to how partially characterized and newly discovered microbial toxins exploit host factors or processes to intoxicate target cells.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
The pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is generally attributed to vascular smooth muscle cell (VSMC) pathologies. However, the role of immune cell-mediated inflammation remains elusive. Single-cell RNA sequencing identified a subset of CX3CR1+ macrophages mainly located in the intima in the aortic roots and ascending aortas of Fbn1C1041G/+ mice, further validated in MFS patients.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
Institute of Food Science and Engineering, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Since the natural supply of iron is low, microorganisms acquire iron by secreting siderophores. is known for its abundant secondary metabolites containing various types of siderophores, including hydroxamate, catecholate, and carboxylate. These siderophores are mainly synthesized through the nonribosomal peptide synthase (NRPS) and non-NRPS pathways and are regulated by ferric uptake regulator and diphtheria toxin regulators.
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