PmiR senses 2-methylisocitrate levels to regulate bacterial virulence in Pseudomonas aeruginosa.

To adapt to changes in environmental cues, Pseudomonas aeruginosa produces an array of virulence factors to survive the host immune responses during infection. Metabolic products contribute to bacterial virulence; however, only a limited number of these signaling receptors have been explored in detail for their ability to modulate virulence in bacteria. Here, we characterize the metabolic pathway of 2-methylcitrate cycle in P. aeruginosa and unveil that PmiR served as a receptor of 2-methylisocitrate (MIC) to govern bacterial virulence. Crystallographic studies and structural-guided mutagenesis uncovered several residues crucial for PmiR's allosteric activation by MIC. We also demonstrated that PmiR directly repressed the pqs quorum-sensing system and subsequently inhibited pyocyanin production. Moreover, mutation of pmiR reduces bacterial survival in a mouse model of acute pneumonia infection. Collectively, this study identified P. aeruginosa PmiR as an important metabolic sensor for regulating expression of bacterial virulence genes to adapt to the harsh environments.

The Anticancer Activity of Indazole Compounds: A Mini Review.

The incidence and mortality of cancer continue to grow since the current medical treatments often fail to produce a complete and durable tumor response and ultimately give rise to therapy resistance and tumor relapse. Heterocycles with potential therapeutic values are of great pharmacological importance, and among them, indazole moiety is a privileged structure in medicinal chemistry. Indazole compounds possess potential anticancer activity, and indazole-based agents such as, axitinib, lonidamine and pazopanib have already been employed for cancer therapy, demonstrating indazole compounds as useful templates for the development of novel anticancer agents. The aim of this review is to present the main aspects of exploring anticancer properties, such as the structural modifications, the structure-activity relationship and mechanisms of action, making an effort to highlight the importance and therapeutic potential of the indazole compounds in the present anticancer agents.

CRISPR/Cas9-mediated knockout of the PDEF gene inhibits migration and invasion of human gastric cancer AGS cells.

Gastric cancer is one of the most common malignant tumors worldwide and has the second highest incidence and mortality rate among malignant tumors in China. Prostate-derived Ets factor (PDEF) is a member of the Ets family of transcription factors. Although PDEF plays an important role in tumorigenesis, its biological function in gastric cancer is still unclear. Here, we evaluated PDEF expression in 30 cases of human gastric carcinoma and the corresponding peritumoral tissues, using immunohistochemistry and immunofluorescence. Significantly higher levels of PDEF were detected in tumors compared to peritumoral tissues. We then investigated PDEF expression in the gastric cancer cell lines SGC and AGS and the normal gastric epithelial cell line GES; The CRISPR/Cas9 genome-editing system was used to knockout PDEF in AGS cells as a model for gastric cancer. Cell proliferation, apoptosis, migration, and invasion of PDEF-knockout AGS cells were evaluated using CCK-8, flow cytometry, scratch wound, and transwell assays, respectively. The results illustrated that PDEF-knockout inhibited AGS cell proliferation, migration, and invasion. Taken together, the results imply that PDEF plays important roles in the proliferation, migration, and invasion of AGS cells and may serve as a new treatment target in gastric cancer.

[Screening of Molluscacidal Microorganisms against Oncomelania hupensis and Their Effect].

Fifteen soil samples were collected from Oncomelania hupensis culture pond in Miluo Schistosomiasis Control and Prevention Base, Hunan Province. Four strains of bacteria were identified to have molluscacidal effects, numbered as B8, B27, B36 and B59. Compared with the fermentation broth groups and bacteria suspension groups, the fermentation supernatant groups of the four strains showed the strongest molluscacidal effect. The fermentation supernatant of B59 strain showed the best molluscacidal effect, with snail mortalit of 73.3% and 96.7% at 48 h and 72 h of treatment, respectively. SDS-PAGE revealed no proteins in fermentation supernatant, fermentation broth and bacteria suspension of B59 strain. Molecular phylogenetic analysis based on ITS sequence showed that the ITS sequence of strain B59 (accession No. KP146144) was 100% homologous to that of the same fragment of Bacillus cereus (accession No. CP001746).