Biophysical characterization and in silico analysis of natural and synthetic compounds targeting Listeria monocytogenes HtrA protease.

HtrA protein is a member of a serine protease family with dual functions as a protease and molecular chaperone. It is a virulence factor in many bacteria, including the food-borne pathogen Listeria monocytogenes (Lm), which induces listeriosis in humans. Hence, inhibitors of LmHtrA protease have great importance in the control of infection.

ADP-heptose attenuates -induced dendritic cell activation.

Sophisticated immune evasion strategies enable to colonize the gastric mucosa of approximately half of the world's population. Persistent infection and the resulting chronic inflammation are a major cause of gastric cancer. To understand the intricate interplay between and host immunity, spatial profiling was used to monitor immune cells in infected gastric tissue.

HtrA-Dependent E-Cadherin Shedding Impairs the Epithelial Barrier Function in Primary Gastric Epithelial Cells and Gastric Organoids.

Impaired E-cadherin (Cdh1) functions are closely associated with cellular dedifferentiation, infiltrative tumor growth and metastasis, particularly in gastric cancer. The class-I carcinogen () colonizes gastric epithelial cells and induces Cdh1 shedding, which is primarily mediated by the secreted bacterial protease high temperature requirement A (HtrA). In this study, we used human primary epithelial cell lines derived from gastroids and mucosoids from different healthy donors to investigate HtrA-mediated Cdh1 cleavage and the subsequent impact on bacterial pathogenesis in a non-neoplastic context.

Implications of silver nanoparticles for infection: modulation of CagA function and signaling.

Background: Helicobacter pylori infection poses a significant health burden worldwide, and its virulence factor CagA plays a pivotal role in its pathogenesis.

Methods: In this study, the interaction between H. pylori-infected AGS cells and silver nanoparticles (AgNPs) was investigated, with a focus on the modulation of CagA-mediated responses, investigated by western blotting.

Bacterial Proteases in Helicobacter pylori Infections and Gastric Disease.

Helicobacter pylori (H. pylori) proteases have become a major focus of research in recent years, because they not only have an important function in bacterial physiology, but also directly alter host cell functions. In this review, we summarize recent findings on extracellular H.

induces a novel form of innate immune memory via accumulation of NF-кB proteins.

is a widespread Gram-negative pathogen involved in a variety of gastrointestinal diseases, including gastritis, ulceration, mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer. Immune responses aimed at eradication of often prove futile, and paradoxically play a crucial role in the degeneration of epithelial integrity and disease progression. We have previously shown that infection of primary human monocytes increases their potential to respond to subsequent bacterial stimuli - a process that may be involved in the generation of exaggerated, yet ineffective immune responses directed against the pathogen.

Inhibition of Listeria Monocytogenes HtrA Protease with Camostat, Gabexate and Nafamostat Mesylates and the Binding Mode of the Inhibitors.

In many bacteria, the High Temperature requirement A (HtrA) protein functions as a chaperone and protease. HtrA is an important factor in stress tolerance and plays a significant role in the virulence of several pathogenic bacteria. Camostat, gabexate and nafamostat mesylates are serine protease inhibitors and have recently shown a great impact in the inhibition studies of SARS-CoV2.

Discovery and Characterization of Synthesized and FDA-Approved Inhibitors of Clostridial and Bacillary Collagenases.

In view of the worldwide antimicrobial resistance (AMR) threat, new bacterial targets and anti-infective agents are needed. Since important roles in bacterial pathogenesis have been demonstrated for the collagenase H and G (ColH and ColG) from , collagenase Q1 and A (ColQ1 and ColA) from represent attractive antivirulence targets. Furthermore, repurposing FDA-approved drugs may assist to tackle the AMR crisis and was addressed in this work.

E-Cadherin Orthologues as Substrates for the Serine Protease High Temperature Requirement A (HtrA).

() expresses the serine protease and chaperone High temperature requirement A (HtrA) that is involved in periplasmic unfolded protein stress response. Additionally, -secreted HtrA directly cleaves the human cell adhesion molecule E-cadherin leading to a local disruption of intercellular adhesions during pathogenesis. HtrA-mediated E-cadherin cleavage has been observed in response to a broad range of pathogens, implying that it is a prevalent mechanism in humans.

Inhibition of Collagenase Q1 of as a Novel Antivirulence Strategy for the Treatment of Skin-Wound Infections.

Despite the progress in surgical techniques and antibiotic prophylaxis, opportunistic wound infections with remain a public health problem. Secreted toxins are one of the main factors contributing to . pathogenicity.

Proteolytic Landscapes in Gastric Pathology and Cancerogenesis.

Gastric cancer is a leading cause of cancer-related death, and a large proportion of cases are inseparably linked to infections with the bacterial pathogen and type I carcinogen . The development of gastric cancer follows a cascade of transformative tissue events in an inflammatory environment. Proteases of host origin as well as -derived proteases contribute to disease progression at every stage, from chronic gastritis to gastric cancer.

High Temperature Requirement A (HtrA) protease of Listeria monocytogenes and its interaction with extracellular matrix molecules.

High Temperature Requirement A (HtrA) was identified as a secreted virulence factor in many pathogenic bacteria, including Listeria monocytogenes. Recently, it was discovered that Helicobacter pylori and Campylobacter jejuni HtrAs can directly cleave the human cell-adhesion molecule E-cadherin, which facilitates bacterial transmigration. HtrAs also interact with extracellular matrix (ECM) molecules.

Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells.

Background: High temperature requirement A (HtrA) is an active serine protease secreted by the group-I carcinogen Helicobacter pylori (H. pylori). The human cell adhesion protein and tumor suppressor E-cadherin (hCdh1) expressed on the surface of gastric epithelial cells was identified as the first HtrA substrate.

CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells.

Background: () colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the virulence factor cytotoxin-associated gene A (CagA) in pathogenesis. The pathogenic activity of CagA is partly regulated by tyrosine phosphorylation of C-terminal Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in host cells.

H. pylori modulates DC functions via T4SS/TNFα/p38-dependent SOCS3 expression.

Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium that chronically infects approximately 50% of the world's human population. While in most cases the infection remains asymptomatic, 10% of infected individuals develop gastric pathologies and 1-3% progress to gastric cancer.

Morphing of Amphipathic Helices to Explore the Activity and Selectivity of Membranolytic Antimicrobial Peptides.

Naturally occurring membranolytic antimicrobial peptides (AMPs) are rarely cell-type selective and highly potent at the same time. Template-based peptide design can be used to generate AMPs with improved properties . Following this approach, 18 linear peptides were obtained by computationally morphing the natural AMP Aurein 2.

-Derived Outer Membrane Vesicles (OMVs): Role in Bacterial Pathogenesis?

Persistent infections with the human pathogen () have been closely associated with the induction and progression of a wide range of gastric disorders, including acute and chronic gastritis, ulceration in the stomach and duodenum, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. The pathogenesis of is determined by a complicated network of manifold mechanisms of pathogen-host interactions, which involves a coordinated interplay of pathogenicity and virulence factors with host cells. While these molecular and cellular mechanisms have been intensively investigated to date, the knowledge about outer membrane vesicles (OMVs) derived from and their implication in bacterial pathogenesis is not well developed.

Dissecting the Helicobacter pylori-regulated transcriptome of B cells.

Persistent infections with the bacterial group-I carcinogen Helicobacter pylori (H. pylori) have been associated with a broad range of gastric disorders, including gastritis, ulceration, gastric cancer or mucosa-associated lymphoid tissue (MALT) lymphoma. Pathogenesis of H.

A novel FRET peptide assay reveals efficient Helicobacter pylori HtrA inhibition through zinc and copper binding.

Helicobacter pylori (H. pylori) secretes the chaperone and serine protease high temperature requirement A (HtrA) that cleaves gastric epithelial cell surface proteins to disrupt the epithelial integrity and barrier function. First inhibitory lead structures have demonstrated the essential role of HtrA in H.

Peptidase PepP is a novel virulence factor of contributing to murine campylobacteriosis.

Mechanisms of host-pathogen interactions resulting in immunopathological responses upon human infection are not completely understood, but the recent availability of murine infection models mimicking key features of campylobacteriosis helps solving this dilemma. During a screen for proteases expressed by , we identified a peptidase of the M24 family as a potential novel virulence factor, which was named PepP. The gene is strongly conserved in various species.

TLR2, TLR4 and TLR10 Shape the Cytokine and Chemokine Release of -Infected Human DCs.

is a stomach pathogen that persistently colonizes the gastric mucosa, often leading to chronic inflammation and gastric pathologies. Although infection with is the primary risk factor for gastric cancer, the underlying mechanisms of pathogen persistence and consequential chronic inflammation are still not well understood. Conventional dendritic cells (cDCs), which are among the first immune cells to encounter in the gastric lining, and the cytokines and chemokines they secrete, contribute to both acute and chronic inflammation Therefore, this study aimed to unravel the contributions of specific signaling pathways within human CD1c cDCs (cDC2s) to the composition of secreted cytokines and chemokines in infection.

Correction: Nanoparticle binding attenuates the pathobiology of gastric cancer-associated Helicobacter pylori.

Correction for 'Nanoparticle binding attenuates the pathobiology of gastric cancer-associated Helicobacter pylori' by Dana Westmeier et al., Nanoscale, 2018, 10, 1453-1463.

The proteolytic activity of Listeria monocytogenes HtrA.

Background: High temperature requirement A (HtrA) is a widely expressed chaperone and serine protease in bacteria. HtrA proteases assemble and hydrolyze misfolded proteins to enhance bacterial survival under stress conditions. Listeria monocytogenes (L.

Tyrosine Kinases in Infections and Gastric Cancer.

() has been identified as a leading cause of gastric cancer, which is one of the most frequent and malignant types of tumor. It is characterized by its rapid progression, distant metastases, and resistance to conventional chemotherapy. A number of receptor tyrosine kinases and non-receptor tyrosine kinases have been implicated in -mediated pathogenesis and tumorigenesis.

Activity and Functional Importance of Helicobacter pylori Virulence Factors.

Helicobacter pylori is a very successful Gram-negative pathogen colonizing the stomach of humans worldwide. Infections with this bacterium can generate pathologies ranging from chronic gastritis and peptic ulceration to gastric cancer. The best characterized H.