Development of the CRISPR-Cas12a system for editing of phages.

is a common opportunistic pathogen. The potential efficacy of phage therapy has attracted the attention of researchers, but efficient gene-editing tools are lacking, limiting the study of their biological properties. Here, we designed a type V CRISPR-Cas12a system for the gene editing of phages.

Characterization, genome analysis, and therapeutic evaluation of a novel Salmonella phage vB_SalS_JNS02: a candidate bacteriophage for phage therapy.

Phage therapy is gaining momentum as an alternative to antibiotics in the treatment of salmonellosis caused by Salmonella. In this study, a novel Salmonella phage, vB_SalS_JNS02, was isolated successfully from poultry farms in Shandong, China. The biological characteristics of vB_SalS_JNS02 were analysed, which revealed a short latent period of approximately 10 min and a burst size of 110 PFU/cell.

Quercitrin Is a Novel Inhibitor of Serovar Typhimurium Type III Secretion System.

The purpose was to screen type III secretory system (T3SS) inhibitors of serovar Typhimurium () from natural compounds. The pharmacological activities and action mechanisms of candidate compounds in vivo and in vitro were systematically studied and analyzed. Using a SipA-β-lactamase fusion reporting system, we found that quercitrin significantly blocked the translocation of SipA into eukaryotic host cells without affecting the growth of bacteria.

Isoflavone glucoside genistin, an inhibitor targeting Sortase A and Listeriolysin O, attenuates the virulence of Listeria monocytogenes in vivo and in vitro.

As a common intracellular facultative anaerobic Gram-positive bacterium, Listeria monocytogenes (L. monocytogenes) exhibits strong resistance to extreme environments, such as low temperature and a wide range of pH values, causing contamination in food production and processing. Sortase A (SrtA) and listeriolysin O (LLO), two crucial virulence factors of L.

Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating infection.

Background: (), as a pandemic foodborne pathogen, severely threatens food security and public health care worldwide, which evolves multiple bacterial virulence factors (such as listeriolysin O, LLO) for manipulating the immune response of -host interactions.

Methods: Hemolysis assay was employed to screen a potential LLO inhibitor and the underlying mechanisms were investigated using molecular dynamics (MD) simulation and oligomerization assay. The effects of candidates on immune response were examined by qRT-PCR and immunoblotting analysis.

Inhibition of the Type III Secretion System of Salmonella enterica Serovar Typhimurium via Treatment with Fraxetin.

The increasingly serious problem of bacterial drug resistance has led to the development of antivirulence agents. The Salmonella enterica serovar Typhimurium pathogenicity island (SPI)-encoded type III secretion system (T3SS) and its effector proteins are important virulence factors for Typhimurium invasion and replication in host cells and for antivirulence drug screening. Fraxetin is isolated from spp.

Harmine, an inhibitor of the type III secretion system of serovar Typhimurium.

New therapeutic strategies for clinical serovar Typhimurium ( Typhimurium) infection are urgently needed due to the generation of antibiotic-resistant bacteria. Inhibition of bacterial virulence has been increasingly regarded as a potential and innovative strategy for the development of anti-infection drugs. pathogenicity island (SPI)-encoded type III secretion system (T3SS) represents a key virulence factor in Typhimurium, and active invasion and replication in host cells is facilitated by the secretion of T3SS effector proteins.

Commercialized artemisinin derivatives combined with colistin protect against critical Gram-negative bacterial infection.

The emergence and spread of the mcr-1 gene and its mutants has immensely compromised the efficient usage of colistin for the treatment of drug-resistant Gram-negative bacterial infection in clinical settings. However, there are currently no clinically available colistin synergis. Here we identify artemisinin derivatives, such as dihydroartemisinin (DHA), that produces a synergistic antibacterial effect with colistin against the majority of Gram-negative bacteria (FIC < 0.

Tannic Acid Inhibits Serovar Typhimurium Infection by Targeting the Type III Secretion System.

serovar Typhimurium ( Typhimurium) is a zoonotic pathogen that can cause food poisoning and diarrhea in both humans and animals worldwide. The pathogenicity island (SPI) genes encoded type III secretion system (T3SS) is important for Typhimurium invasion and replication in host cells. Due to the increasing problem of antibiotic resistance, antibiotic treatment for clinical infection has gradually been limited.

Acacetin Alleviates Virulence Both and via the Inhibition of Listeriolysin O.

is a ubiquitous Gram-positive foodborne pathogen that is responsible for listeriosis in both humans and several animal species. The bacterium secretes a pore-forming cholesterol-dependent cytolysin, listeriolysin O (LLO), a major virulence factor involved in the activation of cellular processes. The ability of LLO to lyse erythrocytes is a measure of LLO activity.

Phloretin potentiates polymyxin E activity against gram-negative bacteria.

Aims: The spread of plasmid-mediated polymyxin resistance has jeopardized the use of polymyxin, the last defender that combats infections caused by multidrug-resistant (MDR) gram-negative pathogens.

Main Methods: In this study, phloretin, as a monomeric compound extracted from natural plants, showed a good synergistic effect with polymyxin E against gram-negative bacteria, as evaluated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and Western blot assays. A model of mice infected by Salmonella sp.

Inhibitory effect of hederagenin on Streptococcus pneumoniae pneumolysin in vitro.

Streptococcus pneumoniae is an important pathogen that causes otitis media, pneumonia, meningitis and bacteremia. As an important virulence factors of S. pneumoniae, pneumolysin (PLY) can penetrate cell membranes and lead to cell lysis and inflammation, which is one of the main causes of infection and damage of S.

Myricetin inhibits the type III secretion system of Salmonella enterica serovar typhimurium by downregulating the Salmonella pathogenic island I gene regulatory pathway.

Based on the in-depth study of type III secretion systems (T3SS) in pathogenic bacteria, approaches targeting T3SS have become new alternative strategies to combat drug-resistant bacterial infections. As an important food-borne pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium) injects effector proteins into host cells through the T3SS to disrupt cell signaling and host responses.

Acacetin inhibits Streptococcus pneumoniae virulence by targeting pneumolysin.

Objectives: Streptococcus pneumoniae (S. pneumoniae) is an important commensal and pathogenic bacterium responsible for pneumonia, meningitis and other invasive diseases. Pneumolysin (PLY) is the major virulence factor that contributes significantly to the interaction between S.

Isoalantolactone restores the sensitivity of gram-negative Enterobacteriaceae carrying MCR-1 to carbapenems.

Polymyxin B has been re-applied to the clinic as the final choice for the treatment of multidrug-resistant gram-negative pathogenic infections, but the use of polymyxin B has been re-assessed because of the emergence and spread of the plasmid-mediated mcr-1 gene. The purpose of this study was to search for an MCR inhibitor synergistically acting with polymyxin to treat the infection caused by this pathogen. In this study, we used the broth microdilution checkerboard method to evaluate the synergistic effect of isoalantolactone (IAL) and polymyxin B on mcr-1-positive Enterobacteriaceae.

Identification of the natural product paeonol derived from peony bark as an inhibitor of the Salmonella enterica serovar Typhimurium type III secretion system.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important zoonotic pathogen in public health and food safety. The type III secretion system (T3SS) encoded by Salmonella pathogenicity island (SPI) is a sophisticated molecular machine that facilitates active invasion, intracellular replication, and host inflammation.

Quercetin, a pneumolysin inhibitor, protects mice against Streptococcus pneumoniae infection.

Pneumolysin (PLY), a pore-forming cytotoxin and a major virulence determinant, is a member of the cholesterol-dependent cytolysin (CDC) family and essential for promoting Streptococcus pneumoniae (S.pneumoniae) infection. Due to the action characteristics of hemolysin itself, the pneumolysin released after killing bacteria with conventional antibiotics still has the ability to damage host cells; therefore, drug treatments directly inhibiting hemolysin activity are the most effective.

Tectorigenin reduces type IV pilus-dependent cell adherence in Clostridium perfringens.

Clostridium perfringens is an anaerobic, Gram-positive bacterium that causes a range of diseases in humans and animals around the globe. The type IV pilus (TFP) system plays a key role in the colonization and invasion of host cells, biofilm formation and gliding motility, which is vital for C. perfringens infection.

Inhibition of the type III secretion system by syringaldehyde protects mice from Salmonella enterica serovar Typhimurium.

The invasiveness of Salmonella enterica serovar Typhimurium (S. Typhimurium) is closely associated with the Salmonella pathogenicity island (SPI)-encoded type Ⅲ secretion system (T3SS), which can directly inject a series of effector proteins into eukaryotic cells to enable bacterial infection. In this study, syringaldehyde was identified as an effective inhibitor of the S.

The effect of the mitochondrial permeability transition pore on apoptosis in Eimeria tenella host cells.

Although the mitochondrial permeability transition pore (MPTP) is associated with cellular apoptosis and necrosis, its effect in host response to Eimeria infections is not well understood. In an effort to better understand the effect of MPTP on apoptosis in Eimeria tenella host cells, an MPTP inhibitor (cyclosporin A) was used to inhibit MPTP opening in vitro. Cecal epithelial cells from chick embryos, which were either treated or non-treated with cyclosporin A, were used as Eimeria tenella host cells.

Calcium homeostasis in mitochondrion-mediated apoptosis of chick embryo cecal epithelial cells induced by Eimeria tenella infection.

In this study, the process of Eimeria tenella-induced apoptosis and the effect of calcium homeostasis were investigated in chick embryo cecal epithelial cells. In particular, we examined cytochrome c release into the cytoplasm, mitochondrial permeability transition pore (MPTP) opening, and changes in [Ca(2+)]c and apoptosis in host cells. Apoptosis, MPTP opening, cytochrome c release, and [Ca(2+)]c in host cells increased following infection.

Relationship between Eimeria tenella development and host cell apoptosis in chickens.

Coccidiosis causes considerable economic losses in the poultry industry. At present, the pathology of coccidiosis is preventable with anticoccidials and vaccination, although at considerable cost to the international poultry industry. The purpose of the present study was to elucidate the relationship between Eimeria tenella development and host cell apoptosis in chickens, which provides a theoretical basis for further study of the injury mechanism of E.