Phosphocholine Antagonizes Listeriolysin O-Induced Host Cell Responses of Listeria monocytogenes.

Background: Bacterial toxins disrupt plasma membrane integrity with multitudinous effects on host cells. The secreted pore-forming toxin listeriolysin O (LLO) of the intracellular pathogen Listeria monocytogenes promotes egress of the bacteria from vacuolar compartments into the host cytosol often without overt destruction of the infected cell. Intracellular LLO activity is tightly controlled by host factors including compartmental pH, redox, proteolytic, and proteostatic factors, and inhibited by cholesterol.

The secRNome of Listeria monocytogenes Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon.

Cellular sensing of bacterial RNA is increasingly recognized as a determinant of host-pathogen interactions. The intracellular pathogen induces high levels of type I interferons (alpha/beta interferons [IFN-α/β]) to create a growth-permissive microenvironment during infection. We previously demonstrated that RNAs secreted by (comprising the secRNome) are potent inducers of IFN-β.

Missing elimination via membrane vesicle shedding contributes to the diminished calcium sensitivity of listeriolysin O.

The lytic capacity of cholesterol-dependent cytolysins is enhanced in the extracellular calcium-free environment through a combination of limited membrane repair and diminished membrane toxin removal. For a typical neurotoxin of the group, pneumolysin, this effect has already been observed at reduced (1 mM) calcium conditions, which are pathophysiologically relevant. Here, we tested another neurotoxin of the group, listeriolysin O from L.

Listeriolysin O Causes ENaC Dysfunction in Human Airway Epithelial Cells.

Pulmonary permeability edema is characterized by reduced alveolar Na⁺ uptake capacity and capillary barrier dysfunction and is a potentially lethal complication of listeriosis. Apical Na⁺ uptake is mainly mediated by the epithelial sodium channel (ENaC) and initiates alveolar liquid clearance. Here we examine how listeriolysin O (LLO), the pore-forming toxin of , impairs the expression and activity of ENaC.

Listeriolysin O Regulates the Expression of Optineurin, an Autophagy Adaptor That Inhibits the Growth of Listeria monocytogenes.

Autophagy, a well-established defense mechanism, enables the elimination of intracellular pathogens including . Host cell recognition results in ubiquitination of . and interaction with autophagy adaptors p62/SQSTM1 and NDP52, which target bacteria to autophagosomes by binding to microtubule-associated protein 1 light chain 3 (LC3).

Epithelial Sodium Channel-α Mediates the Protective Effect of the TNF-Derived TIP Peptide in Pneumolysin-Induced Endothelial Barrier Dysfunction.

Background: is a major etiologic agent of bacterial pneumonia. Autolysis and antibiotic-mediated lysis of pneumococci induce release of the pore-forming toxin, pneumolysin (PLY), their major virulence factor, which is a prominent cause of acute lung injury. PLY inhibits alveolar liquid clearance and severely compromises alveolar-capillary barrier function, leading to permeability edema associated with pneumonia.

ActA of Listeria monocytogenes and Its Manifold Activities as an Important Listerial Virulence Factor.

Listeria monocytogenes is a ubiquitously occurring gram-positive bacterium in the environment that causes listeriosis, one of the deadliest foodborne infections known today. It is a versatile facultative intracellular pathogen capable of growth within the host's cytosolic compartment. Following entry into the host cell, L.

Diverse roles of endoplasmic reticulum stress sensors in bacterial infection.

Bacterial infection often leads to cellular damage, primarily marked by loss of cellular integrity and cell death. However, in recent years, it is being increasingly recognized that, in individual cells, there are graded responses collectively termed cell-autonomous defense mechanisms that induce cellular processes designed to limit cell damage, enable repair, and eliminate bacteria. Many of these responses are triggered not by detection of a particular bacterial effector or ligand but rather by their effects on key cellular processes and changes in homeostasis induced by microbial effectors when recognized.

Cell-autonomous responses in Listeria monocytogenes infection.

Listeria monocytogenes is a facultative intracellular bacterium causing listeriosis, a food-borne infection with a high mortality rate. The mechanisms and the role of cells and tissular components in generating protective adaptive immune responses are well studied, and cell biological studies provide a detailed understanding of the processes targeted by the bacterial products. Much less is known of the cellular responses activated to limit infection in individual cells when confronted with stress or infection.

Pneumococcal hydrogen peroxide-induced stress signaling regulates inflammatory genes.

Microbial infections can induce aberrant responses in cellular stress pathways, leading to translational attenuation, metabolic restriction, and activation of oxidative stress, with detrimental effects on cell survival. Here we show that infection of human airway epithelial cells with Streptococcus pneumoniae leads to induction of endoplasmic reticulum (ER) and oxidative stress, activation of mitogen-associated protein kinase (MAPK) signaling pathways, and regulation of their respective target genes. We identify pneumococcal H2O2 as the causative agent for these responses, as both catalase-treated and pyruvate oxidase-deficient bacteria lacked these activities.

Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction.

Rationale: Antibiotic treatment of patients infected with G(-) or G(+) bacteria promotes release of the toxins lipopolysaccharide (LPS) and pneumolysin (PLY) in their lungs. Growth Hormone-releasing Hormone (GHRH) agonist JI-34 protects human lung microvascular endothelial cells (HL-MVEC), expressing splice variant 1 (SV-1) of the receptor, from PLY-induced barrier dysfunction. We investigated whether JI-34 also blunts LPS-induced hyperpermeability.

Activation of the unfolded protein response by Listeria monocytogenes.

The endoplasmic reticulum (ER) responds to perturbation of homeostasis with stress. To maintain ER function, a signalling-circuitry has evolved which, when engaged, attempts to reduce a surplus of unfolded proteins by triggering the unfolded protein response (UPR). Several studies have implicated UPR in viral infections, neurodegenerative disorders and metabolic diseases but UPR has not yet been widely linked to bacterial infections.