An Aerolysin-like Pore-Forming Protein Complex Targets Viral Envelope to Inactivate Herpes Simplex Virus Type 1.

Because most of animal viruses are enveloped, cytoplasmic entry of these viruses via fusion with cellular membrane initiates their invasion. However, the strategies in which host cells counteract cytoplasmic entry of such viruses are incompletely understood. Pore-forming toxin aerolysin-like proteins (ALPs) exist throughout the animal kingdom, but their functions are mostly unknown.

A secreted pore-forming protein modulates cellular endolysosomes to augment antigen presentation.

Bacterial pore-forming toxin aerolysin-like proteins are widely distributed in animals and plants. Emerging evidence supports their roles in host innate immunity, but their direct actions in adaptive immunity remain elusive. In this study, we found that βγ-CAT, an aerolysin-like protein and trefoil factor complex identified in the frog Bombina maxima, modulated several steps of endocytic pathways during dendritic cell antigen presentation.

A cellular endolysosome-modulating pore-forming protein from a toad is negatively regulated by its paralog under oxidizing conditions.

Endolysosomes are key players in cell physiology, including molecular exchange, immunity, and environmental adaptation. They are the molecular targets of some pore-forming aerolysin-like proteins (ALPs) that are widely distributed in animals and plants and are functionally related to bacterial toxin aerolysins. βγ-CAT is a complex of an ALP (BmALP1) and a trefoil factor (BmTFF3) in the firebelly toad ().

Geraniol targets K1.3 ion channel and exhibits anti-inflammatory activity in vitro and in vivo.

Naturally occurring monoterpenes are known for their various pharmacological activities including anti-inflammation. K1.3 ion channel is a voltage-gated potassium channel and has been validated as a drug target for autoimmune and chronic inflammatory diseases like psoriasis.

Endogenous pore-forming protein complex targets acidic glycosphingolipids in lipid rafts to initiate endolysosome regulation.

Bacterial pore-forming toxin aerolysin-like proteins (ALPs) are widely distributed in animals and plants. However, functional studies on these ALPs remain in their infancy. βγ-CAT is the first example of a secreted pore-forming protein that functions to modulate the endolysosome pathway via endocytosis and pore formation on endolysosomes.

Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing.

Background: Nonscar wound healing is a desirable treatment for cutaneous wounds worldwide. Peptide OH-CATH30 (OH30) from king cobra can selectively regulate the innate immunity and create an anti-inflammatory micro-environment which might benefit nonscar wound healing.

Purpose: To overcome the enzymatic digestion and control release of OH30, OH30 encapsulated in carboxymethyl chitosan nanoparticles (CMCS-OH30 NP) were prepared and their effects on wound healing were evaluated.

Pore-forming toxin-like protein complex expressed by frog promotes tissue repair.

Tissue repair is a highly dynamic process, and the immediate onset of acute inflammation has been considered necessary for repair. Pore-forming proteins are important, both in pathogen invasion and host immunity. However, their roles in wound healing and tissue repair are unclear.

A high concentration of DMSO activates caspase-1 by increasing the cell membrane permeability of potassium.

Dimethyl sulfoxide (DMSO) is widely used in the laboratory and in clinical situations because it is soluble in both aqueous and organic media and can be used to treat many types of diseases. Thus, it is meaningful to assess the comprehensive and in-depth biological activities of DMSO. Here, we showed that a high concentration of DMSO induced pro-inflammatory cytokine interleukin-1β (IL-1β) secretion from the monocytic cell line THP-1.

Host Pore-Forming Protein Complex Neutralizes the Acidification of Endocytic Organelles to Counteract Intracellular Pathogens.

Many intracellular pathogens invade cells via endocytic organelles and have adapted to the drop in pH along the endocytic pathway. However, the strategy by which the host cell counteracts this pathogen adaptation remains unclear. βγ-CAT is an aerolysin-like pore-forming protein and trefoil factor complex in the frog Bombina maxima.

Host-derived, pore-forming toxin-like protein and trefoil factor complex protects the host against microbial infection.

Aerolysins are virulence factors belonging to the bacterial β-pore-forming toxin superfamily. Surprisingly, numerous aerolysin-like proteins exist in vertebrates, but their biological functions are unknown. βγ-CAT, a complex of an aerolysin-like protein subunit (two βγ-crystallin domains followed by an aerolysin pore-forming domain) and two trefoil factor subunits, has been identified in frogs (Bombina maxima) skin secretions.

Prohibitin is involved in the activated internalization and degradation of protease-activated receptor 1.

The protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor that is irreversibly activated by either thrombin or metalloprotease 1. Due this irrevocable activation, activated internalization and degradation are critical for PAR1 signaling termination. Prohibitin (PHB) is an evolutionarily conserved, ubiquitously expressed, pleiotropic protein and belongs to the stomatin/prohibitin/flotillin/HflK/C (SPFH) domain family.

Therapeutic potential of the antimicrobial peptide OH-CATH30 for antibiotic-resistant Pseudomonas aeruginosa keratitis.

The therapeutic potential of antimicrobial peptides (AMPs) has been evaluated in many infectious diseases. However, the topical application of AMPs for ocular bacterial infection has not been well investigated. The AMP OH-CATH30, which was identified in the king cobra, exhibits potent antimicrobial activity.

Naturally occurring antimicrobial peptide OH-CATH30 selectively regulates the innate immune response to protect against sepsis.

Sepsis, which is a systemic inflammatory response that follows a bacterial infection, has a high mortality rate and limited therapeutic options. Here we show that the antimicrobial peptide OH-CATH30, which naturally occurs in snake, selectively regulates the innate immune response to protect mice from lethal sepsis. The administration of OH-CATH30 significantly improves the survival rate of mice infected by antibiotic-susceptible and -resistant pathogens, including Escherichia coli , Pseudomonas aeruginosa , and Staphylococcus aureus .

Adenosine-5'-triphosphate (ATP) protects mice against bacterial infection by activation of the NLRP3 inflammasome.

It has been established that Adenosine-5'-triphosphate (ATP) can activate the NLRP3 inflammasome. However, the physiological effect of extracellular ATP on NLRP3 inflammasome activation has not yet been investigated. In the present study, we found that ATP was indeed released during bacterial infection.

Efficacy of OH-CATH30 and its analogs against drug-resistant bacteria in vitro and in mouse models.

Antimicrobial peptides (AMPs) have been considered alternatives to conventional antibiotics for drug-resistant bacterial infections. However, their comparatively high toxicity toward eukaryotic cells and poor efficacy in vivo hamper their clinical application. OH-CATH30, a novel cathelicidin peptide deduced from the king cobra, possesses potent antibacterial activity in vitro.

Two bacterial infection models in tree shrew for evaluating the efficacy of antimicrobial agents.

Animal models are essential for the development of new anti-infectious drugs. Although some bacterial infection models have been established in rodents, small primate models are rare. Here, we report on two bacterial infection models established in tree shrew (Tupaia belangeri chinensis).