Chemical and Biological Threats to Public Safety
Frank A. Barile in Barile’s Clinical Toxicology, 2019
The agents discussed here fall into three major classes of microorganisms: bacteria,* rickettsia, and viruses. In some cases, hazardous bacterial toxins are also produced as by-products of their pathogenic metabolism. To aid in understanding the pathogenic features of infectious agents, several tables are included. Table 34.2 describes the biological features of Category A agents. Table 34.3 outlines the clinical aspects of the same Category A organisms, and Table 34.4 defines and describes signs, symptoms, and syndromes associated with the infectious agents. Incubation periods, duration of illnesses, means of transmission, treatment, and prognosis are also noted for each of the organisms.
Procoagulant Activity in Gastroenterology
Gary A. Levy, Edward H. Cole in Procoagulant Activity in Health and Disease, 2019
There is a further group of conditions which bear distinct similarities to colitis associated with E. coli 0157.H7 infection. Whitehead82 has grouped these under the heading of ischemic enterocolitis; they include necrotizing enterocolitis, uremic colitis, postoperative enterocolitis, staphylococcal enterocolitis, and pseudomembranous colitis. These are not associated with occlusive large vessel disease and are thought to be an expression of the intravascular coagulation syndrome.82 Furthermore, Whitehead suggests that ulceration of the mucosa in these conditions is secondary to microvascular injury in these cases. Thrombosis involving the apical capillary plexus of the mucosa is the characteristic early histological lesion of this group of conditions. Capillary thrombi are present before mucosal necrosis: later shedding of the epithelium is associated with the formation of pseudomembranous plaques consisting of fibrin, mucus, and necrotic epithelial debris. Bacterial toxins have been implicated in the pathogenesis of a number of these conditions.83 One could speculate that the induction of both endothelial cell and monocyte procoagulant activity is responsible for the fibrinous reaction that is observed. However, to date, no data exist to support such a contention.
Neuropathogenesis of viral infections
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
Most microorganisms are known to produce toxic substances. For example, bacterial toxins include cholera toxin, botulinum toxin, tetanus toxoid, etc. Prion proteins have been studied extensively with regards to their neurotoxic properties. Similarly, viral products may also be toxic. Although virotoxins have been best characterized for HIV gene products, it is increasingly clear that several other viruses also produce toxic gene products (Table 2.5). For example, the rabies virus [53] envelope glycoprotein and the measles virus hemagglutinin glycoprotein [54] have sequence homology to snake venom neurotoxins and the fusion domain of influenza virus has a striking similarity to the neurotoxic domain of amyloid beta peptide [55]. A common theme emerges in these viruses, in that often it is the envelope and the transactivating viral genes that are toxic. These viral proteins may interact with neurons and glial cells to disrupt their function.
Healthy Intestinal Function Relies on Coordinated Enteric Nervous System, Immune System, and Epithelium Responses
Published in Gut Microbes, 2021
Fatima B. Saldana-Morales, Dasom V. Kim, Ming-Ting Tsai, Gretchen E. Diehl
Toxins produced by enteric pathogens are secreted factors that aid in the successful invasion of host cells and are an important etiology of pathogen-induced diarrheal diseases.101 Once a pathogen is attached to IECs, secreted toxins regulate water and electrolyte flux, form pores on target cells, regulate host cell protein synthesis, or affect the actin cytoskeleton to disrupt the intestinal epithelial barrier.102 For example, bacterial toxins from Clostridium spp. disrupt intestinal tight junctions by altering Rho GTPases and by interfering with actin ATPase activity.103,104 There are two main toxins produced by Clostridium difficile: TcdA and TcdB. Both inactivate Rho proteins and lead to increased intestinal permeability, disruption of chemotaxis, and cytoskeletal depolymerization.105 They can also disorganize F-actin and dissociate tight junction proteins occludin, ZO-1 and ZO-2.106 Similarly, C. botulinum C3 toxin disassembles actin filaments and disrupts tight junctions.103 By disrupting the host mucosal barrier, toxins facilitate pathogen colonization of the host intestine. Toxins can also induce protection. TcdA and TcdB also activate IEC apoptosis which limits the spread of C. difficile infection in vivo.107
Membrane protective role of autophagic machinery during infection of epithelial cells by Candida albicans
Published in Gut Microbes, 2022
Pierre Lapaquette, Amandine Ducreux, Louise Basmaciyan, Tracy Paradis, Fabienne Bon, Amandine Bataille, Pascale Winckler, Bernhard Hube, Christophe d’Enfert, Audrey Esclatine, Elisabeth Dubus, Marie-Agnès Bringer, Etienne Morel, Frédéric Dalle
Contribution of some autophagy-related proteins (ATG16L1, ATG5, and ATG12) in lysosomal exocytosis was recently highlighted in the context of host cell infection by the Gram-positive pathogenic bacterium Listeria monocytogenes.46 Cells lacking these ATG proteins were unable to trigger lysosomal membrane exocytosis for the repair of membrane damage induced by bacterial pore-forming toxins (LLO and PLY). As a result, an increase in sensitivity of cells to bacterial toxins was observed.46 Interestingly, we report herein similar observations showing that plasma membrane damage induced by C. albicans correlates with (i) a strong decrease in lysosomal membrane exocytosis as observed in ATG16L1- and Atg5-deficient cells and (ii) an increase sensitivity of these deficient cells to C. albicans-mediated cell death. This plasma membrane damage might result from the mechanical stress applied by the fungal active penetration in association with secreted factors (including Saps) already reported to alter the host plasma membrane.1
Reversible cross-tolerance to platelet-activating factor signaling by bacterial toxins
Published in Platelets, 2021
Kandahalli Venkataranganayaka Abhilasha, Mosale Seetharam Sumanth, Anita Thyagarajan, Ravi Prakash Sahu, Kempaiah Kemparaju, Gopal Kedihithlu Marathe
Bacterial toxins are implicated in the pathogenesis of many inflammatory diseases like endotoxemia [1–4]. Such toxins are recognized by the Toll-like receptors (TLRs) [5,6]. Lipopolysaccharide (LPS), an abundant and widely employed endotoxin demonstrates its pro-inflammatory actions via TLR-4 [7] while lipoteichoic acid (LTA), bacterial lipoproteins such as Braun lipoprotein (BLP), and its synthetic analogue Pam3CSK4 signal through TLR-2 [8,9]. Activation of both TLR-4 and TLR-2 leads to signaling via mitogen-activated protein kinases (MAPKs) [10,11], and upregulation of nuclear factor kappa B (NF-κB) driven pro-inflammatory gene products such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, IL-6, IL-8, cyclooxygenase type 2 (COX-2), etc [2,12]. Accordingly, bacteria deficient in LPS are less toxic to mice [13].
Related Knowledge Centers
- Bacteria
- Botulinum Toxin
- Cell Biology
- Clostridium
- Clostridium Botulinum
- Exotoxin
- Lipopolysaccharide
- Toxin
- Virus
- Neuroscience