Signal Transduction and Endocytosis of Rhizobia in the Host Cells

To establish infection, pathogens secrete virulence factors, such as protein kinases and phosphatases, to modulate the signal transduction pathways used by host cells to initiate immune response. The protein MAP3893c is annotated in the genome sequence ofMycobacterium aviumsubspeciesparatuberculosis(MAP), the causative agent of Johne’s disease, as the serine/threonine protein kinase G (PknG). In this work, we report that PknG is a functional kinase that is secreted within macrophages at early stages of infection. The antigen is able to induce an immune response from cattle exposed to MAP in the form of interferon gamma production after stimulation of whole blood with PknG. These findings suggest that PknG may contribute to the pathogenesis of MAP by phosphorylating macrophage signalling and/or adaptor molecules as observed with other pathogenic mycobacterial species.

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Rapid modulation of electrolyte transport in Caco-2 cell monolayers by enteropathogenic Escherichia coli (EPEC) infection

Gut ◽

10.1136/gut.42.2.200 ◽

1998 ◽

Vol 42 (2) ◽

pp. 200-207 ◽

Cited By ~ 64

Author(s):

G K Collington ◽

I W Booth ◽

S Knutton

Keyword(s):

Escherichia Coli ◽

Signal Transduction ◽

Short Circuit ◽

Electrolyte Transport ◽

Host Cells ◽

Ussing Chambers ◽

Cell Monolayers ◽

Initial Adhesion ◽

Rapid Modulation

Background and aims—The pathophysiology of enteropathogenic Escherichia coli (EPEC) diarrhoea remains uncertain. EPEC adhere to enterocytes and transduce signals which produce a characteristic “attaching and effacing” (A/E) lesion in the brush border membrane. The present in vitro study was designed to determine whether signal transduction by EPEC also influences electrolyte transport.Methods—Caco-2 cell monolayers were rapidly infected with wild type EPEC strain E2348/69, or the signal transduction-defective mutant 14.2.1(1), and mounted in Ussing chambers.Results—Strain E2348/69 stimulated a rapid but transient increase in short circuit current (Isc) which coincided with A/E lesion formation; this Isc response was absent on infection with strain 14.2.1(1). While the initial rise inIsc induced by E2348/69 was partially (∼35%) dependent on chloride, the remainder possibly represents an influx of sodium and amino acid(s) across the apical membrane.Conclusions—The study directly shows that, after initial adhesion, EPEC induce major alterations in host cell electrolyte transport. The observed Isc responses indicate a rapid modulation of electrolyte transport in Caco-2 cells by EPEC, including stimulation of chloride secretion, for which signal transduction to host cells is a prerequisite.

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Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites.

Journal of Experimental Medicine ◽

10.1084/jem.177.1.145 ◽

1993 ◽

Vol 177 (1) ◽

pp. 145-153 ◽

Cited By ~ 325

Author(s):

L Schofield ◽

F Hackett

Keyword(s):

Signal Transduction ◽

Interleukin 1 ◽

Host Cells ◽

Rational Basis ◽

Cytokine Release ◽

Cytokine Induction ◽

Kinase C ◽

Pathogenic Process ◽

Necrosis Factor

In this study, we have identified a dominant glycolipid toxin of Plasmodium falciparum. It is a glycosylphosphatidylinositol (GPI). The parasite GPI moiety, free or associated with protein, induces tumor necrosis factor and interleukin 1 production by macrophages and regulates glucose metabolism in adipocytes. Deacylation with specific phospholipases abolishes cytokine induction, as do inhibitors of protein kinase C. When administered to mice in vivo the parasite GPI induces cytokine release, a transient pyrexia, and hypoglycemia. When administered with sensitizing agents it can elicit a profound and lethal cachexia. Thus, the GPI of Plasmodium is a potent glycolipid toxin that may be responsible for a novel pathogenic process, exerting pleiotropic effects on a variety of host cells by substituting for the endogenous GPI-based second messenger/signal transduction pathways. Antibody to the GPI inhibits these toxic activities, suggesting a rational basis for the development of an antiglycolipid vaccine against malaria.

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Interactions and Signal Transduction Pathways Involved during Central Nervous System Entry by Neisseria meningitidis across the Blood–Brain Barriers

International Journal of Molecular Sciences ◽

10.3390/ijms21228788 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8788

Author(s):

Julia Borkowski ◽

Horst Schroten ◽

Christian Schwerk

Keyword(s):

Signal Transduction ◽

Central Nervous System ◽

Nervous System ◽

Neisseria Meningitidis ◽

Severe Disease ◽

Blood Stream ◽

Brain Parenchyma ◽

Host Cells ◽

Signal Transduction Pathways ◽

Blood Brain

The Gram-negative diplococcus Neisseria meningitidis, also called meningococcus, exclusively infects humans and can cause meningitis, a severe disease that can lead to the death of the afflicted individuals. To cause meningitis, the bacteria have to enter the central nervous system (CNS) by crossing one of the barriers protecting the CNS from entry by pathogens. These barriers are represented by the blood–brain barrier separating the blood from the brain parenchyma and the blood–cerebrospinal fluid (CSF) barriers at the choroid plexus and the meninges. During the course of meningococcal disease resulting in meningitis, the bacteria undergo several interactions with host cells, including the pharyngeal epithelium and the cells constituting the barriers between the blood and the CSF. These interactions are required to initiate signal transduction pathways that are involved during the crossing of the meningococci into the blood stream and CNS entry, as well as in the host cell response to infection. In this review we summarize the interactions and pathways involved in these processes, whose understanding could help to better understand the pathogenesis of meningococcal meningitis.

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Bordetella pertussis filamentous hemagglutinin interacts with a leukocyte signal transduction complex and stimulates bacterial adherence to monocyte CR3 (CD11b/CD18).

Journal of Experimental Medicine ◽

10.1084/jem.180.4.1225 ◽

1994 ◽

Vol 180 (4) ◽

pp. 1225-1233 ◽

Cited By ~ 103

Author(s):

Y Ishibashi ◽

S Claus ◽

D A Relman

Keyword(s):

Signal Transduction ◽

Bordetella Pertussis ◽

Whooping Cough ◽

Bacterial Pathogen ◽

Binding Activity ◽

Host Cells ◽

Bacterial Surface ◽

Filamentous Hemagglutinin ◽

Complement Receptor 3 ◽

Leukocyte Response

Bordetella pertussis, the causative agent of whooping cough, adheres to human monocytes/macrophages by means of a bacterial surface-associated protein, filamentous hemagglutinin (FHA) and the leukocyte integrin, complement receptor 3 (CR3, alpha M beta 2, CD11b/CD18). We show that an FHA Arg-Gly-Asp site induces enhanced B. pertussis binding to monocytes, and that this enhancement is blocked by antibodies directed against CR3. Enhancement requires a monocyte signal transduction complex, composed of leukocyte response integrin (alpha? beta 3) and integrin-associated protein (CD47). This complex is known to upregulate CR3 binding activity. Thus, a bacterial pathogen enhances its own attachment to host cells by coopting a host cell signaling pathway.

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Crosstalk between E-Cadherin/β-Catenin and NF-κB Signaling Pathways: The Regulation of Host-Pathogen Interaction during Leptospirosis

International Journal of Molecular Sciences ◽

10.3390/ijms222313132 ◽

2021 ◽

Vol 22 (23) ◽

pp. 13132

Author(s):

Shen-Hsing Hsu ◽

Li-Fang Chou ◽

Chung-Hung Hong ◽

Ming-Yang Chang ◽

Chung-Ying Tsai ◽

...

Keyword(s):

Signal Transduction ◽

Signal Transduction Pathway ◽

Kidney Injury ◽

Host Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Transduction Pathway ◽

Pathogenic Leptospira ◽

Lrr Domain ◽

Leptospira Species ◽

E Cadherin

Approximately 1 million cases of leptospirosis, an emerging infectious zoonotic disease, are reported each year. Pathogenic Leptospira species express leucine-rich repeat (LRR) proteins that are rarely expressed in non-pathogenic Leptospira species. The LRR domain-containing protein family is vital for the virulence of pathogenic Leptospira species. In this study, the biological mechanisms of an essential LRR domain protein from pathogenic Leptospira were examined. The effects of Leptospira and recombinant LRR20 (rLRR20) on the expression levels of factors involved in signal transduction were examined using microarray, quantitative real-time polymerase chain reaction, and western blotting. The secreted biomarkers were measured using an enzyme-linked immunosorbent assay. rLRR20 colocalized with E-cadherin on the cell surface and activated the downstream transcription factor β-catenin, which subsequently promoted the expression of MMP7, a kidney injury biomarker. Additionally, MMP7 inhibitors were used to demonstrate that the secreted MMP7 degrades surface E-cadherin. This feedback inhibition mechanism downregulated surface E-cadherin expression and inhibited the colonization of Leptospira. The degradation of surface E-cadherin activated the NF-κB signal transduction pathway. Leptospirosis-associated acute kidney injury is associated with the secretion of NGAL, a downstream upregulated biomarker of the NF-κB signal transduction pathway. A working model was proposed to illustrate the crosstalk between E-cadherin/β-catenin and NF-κB signal transduction pathways during Leptospira infection. Thus, rLRR20 of Leptospira induces kidney injury in host cells and inhibits the adhesion and invasion of Leptospira through the upregulation of MMP7 and NGAL.

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Attaching and effacing of host cells by enteropathogenicEscherichia coliin the absence of detectable tyrosine kinase mediated signal transduction

Microbial Pathogenesis ◽

10.1006/mpat.1996.0051 ◽

1996 ◽

Vol 21 (3) ◽

pp. 157-171 ◽

Cited By ~ 23

Author(s):

Ronald P. Rabinowitz ◽

Li-Ching Lai ◽

Karen Jarvis ◽

Timothy K. McDaniel ◽

James B. Kaper ◽

...

Keyword(s):

Signal Transduction ◽

Tyrosine Kinase ◽

Host Cells

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Regulation of the Type III Secretion System in Phytopathogenic Bacteria

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-19-1159 ◽

2006 ◽

Vol 19 (11) ◽

pp. 1159-1166 ◽

Cited By ~ 134

Author(s):

Xiaoyan Tang ◽

Yanmei Xiao ◽

Jian-Min Zhou

Keyword(s):

Signal Transduction ◽

Hypersensitive Response ◽

Type Iii Secretion ◽

Pathogenic Bacteria ◽

Type Iii Secretion System ◽

Secretion System ◽

Host Cells ◽

Plant Pathogenic Bacteria ◽

Type Iii ◽

Hrp Genes

The type III secretion system (TTSS) is a specialized protein secretion machinery used by numerous gram-negative bacterial pathogens of animals and plants to deliver effector proteins directly into the host cells. In plant-pathogenic bacteria, genes encoding the TTSS were discovered as hypersensitive response and pathogenicity (hrp) genes, because mutation of these genes typically disrupts the bacterial ability to cause diseases on host plants and to elicit hypersensitive response on nonhost plants. The hrp genes and the type III effector genes (collectively called TTSS genes hereafter) are repressed in nutrient-rich media but induced when bacteria are infiltrated into plants or incubated in nutrient-deficient inducing media. Multiple regulatory components have been identified in the plant-pathogenic bacteria regulating TTSS genes under various conditions. In Ralstonia solanacearum, several signal transduction components essential for the induction of TTSS genes in plants are dispensable for the induction in inducing medium. In addition to the inducing signals, recent studies indicated the presence of negative signals in the plant regulating the Pseudomonas syringae TTSS genes. Thus, the levels of TTSS gene expression in plants likely are determined by the interactions of multiple signal transduction pathways. Studies of the hrp regulons indicated that TTSS genes are coordinately regulated with a number of non-TTSS genes.

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Analysis and construction of pathogenicity island regulatory pathways in Salmonella enterica serovar Typhi

Journal of Integrative Bioinformatics ◽

10.1515/jib-2010-145 ◽

2010 ◽

Vol 7 (1) ◽

Cited By ~ 3

Author(s):

Su Yean Ong ◽

Fui Ling Ng ◽

Siti Suriawati Badai ◽

Anton Yuryev ◽

Maqsudul Alam

Keyword(s):

Signal Transduction ◽

Protein Interactions ◽

Salmonella Enterica ◽

Environmental Changes ◽

Host Cells ◽

Extraction Technology ◽

Regulatory Pathways ◽

Salmonella Enterica Serovar Typhi ◽

Interaction Database ◽

Efficient Detection

SummarySignal transduction through protein-protein interactions and protein modifications are the main mechanisms controlling many biological processes. Here we described the implementation of MedScan information extraction technology and Pathway Studio software (Ariadne Genomics Inc.) to create a Salmonella specific molecular interaction database. Using the database, we have constructed several signal transduction pathways in Salmonella enterica serovar Typhi which causes Typhoid Fever, a major health threat especially in developing countries. S. Typhi has several pathogenicity islands that control rapid switching between different phenotypes including adhesion and colonization, invasion, intracellular survival, proliferation, and biofilm formation in response to environmental changes. Understanding of the detailed mechanism for S. Typhi survival in host cells is necessary for development of efficient detection and treatment of this pathogen. The constructed pathways were validated using publically available gene expression microarray data for Salmonella.

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Ca2+ release from host intracellular stores and related signal transduction during Campylobacter jejuni 81-176 internalization into human intestinal cells

Microbiology ◽

10.1099/mic.0.27866-0 ◽

2005 ◽

Vol 151 (9) ◽

pp. 3097-3105 ◽

Cited By ~ 35

Author(s):

Lan Hu ◽

Richard B. Raybourne ◽

Dennis J. Kopecko

Keyword(s):

Signal Transduction ◽

Campylobacter Jejuni ◽

Cell Signalling ◽

Specific Inhibitor ◽

Diarrhoeal Disease ◽

Eukaryotic Cell ◽

Host Cells ◽

Intestinal Cells ◽

Acetoxymethyl Ester ◽

Calmodulin Antagonist

Campylobacter jejuni is the leading bacterial cause of human diarrhoeal disease in many parts of the world, including the USA. The ability of C. jejuni to invade the host intestinal epithelium is an important determinant of virulence. A common theme among pathogenic invasive micro-organisms is their ability to usurp the eukaryotic cell-signalling systems both to allow for invasion and to trigger disease pathogenesis. Ca2+ is very important in a great variety of eukaryotic cell-signalling processes (e.g. calmodulin-activated enzymes, nuclear transcriptional upregulation, and cytoskeletal rearrangements). This study analyses the effects of Ca2+ availability on invasion of human INT407 intestinal epithelial cells by C. jejuni strain 81-176. The ability of C. jejuni to invade INT407 cells was not blocked by chelation of any remaining extracellular Ca2+ from host cells incubated in Ca2+-free, serum-free media. In contrast, C. jejuni invasion was markedly reduced either by chelating host intracellular Ca2+ with 1,2-bis-(2-)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA, AM) or by blocking the release of Ca2+ from intracellular stores with dantrolene or U73122. Moreover, Bay K8644, a plasma-membrane Ca2+-channel agonist, was observed to stimulate C. jejuni invasion, presumably by increasing host intracellular free Ca2+ levels. Measurement of host-cell cytosolic Ca2+ via spectrofluorimetry and fluorescence microscopy revealed an increase in Ca2+ from 10 min post-infection. Monolayer pretreatment with either a calmodulin antagonist or a specific inhibitor of protein kinase C was found to cause a marked reduction in C. jejuni invasion, suggesting roles for these Ca2+-activated modulators in signal-transduction events involved in C. jejuni invasion. These results demonstrate that C. jejuni induces the mobilization of Ca2+ from host intracellular stores, which is an essential step in the invasion of intestinal cells by this pathogen.

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