Bilobetin attenuates Staphylococcus aureus virulence by targeting Von Willebrand factor-binding protein and staphylocoagulase.

Staphylococcus aureus (S. aureus) induces a variety of infectious diseases in humans and animals and is responsible for hospital- and community-acquired infections. The aim of this study was to investigate how bilobetin, a natural compound, attenuates S. aureus virulence by inhibiting two key virulence factors, von Willebrand factor-binding protein (vWbp) and staphylocoagulase (Coa). The results showed that bilobetin inhibited Coa- or vWbp-induced coagulation without affecting S. aureus proliferation. The Western blotting and fluorescence quenching assays indicated that bilobetin did not affect the expression of vWbp and Coa but directly bound to the proteins with KA values of 1.66 × 104 L/mol and 1.04 × 104 L/mol, respectively. To gain further insight into the mechanism of interaction of bilobetin with these virulence factors, we performed molecular docking and point mutation assays, which indicated that the TYR-6 and TYR-18 residues on vWbp and the ALA-190 and ASP-189 residues on Coa were essential for the binding of bilobetin. In addition, the in vivo studies showed that bilobetin ameliorated lung tissue damage and inflammation caused by S. aureus, thereby improving the survival of mice. Furthermore, the use of bilobetin as an adjuvant in combination with vancomycin was more effective in the treatment of a mouse model of pneumonia. Taken together, bilobetin had a dual inhibitory effect on vWbp and Coa by reducing the virulence of S. aureus, suggesting that it is a viable lead compound against S. aureus infections.

7,8-Dihydroxyflavone attenuates the virulence of Staphylococcus aureus by inhibiting alpha-hemolysin.

Staphylococcus aureus (S. aureus), a Gram-positive bacteria, is an incurable cause of hospital and community-acquired infections. Inhibition bacterial virulence is a viable strategy against S. aureus infections based on the multiple virulence factors secreted by S. aureus. Alpha-hemolysin (Hla) plays a crucial role in bacteria virulence without affecting bacterial viability. Here, we identified that 7,8-Dihydroxyflavone (7,8-DHF), a natural compound, was able to decrease the expression of and did not affect the in vitro growth of S. aureus USA300 at a concentration of 32 µg/mL. It was verified by western blot and RT-qPCR that the natural compound could inhibit the transcription and translation of Hla. Further mechanism studies revealed that 7,8-DHF has a negative effect on transcriptional regulator agrA and RNAIII, preventing the upregulation of virulence gene. Cytotoxicity assays showed that 7,8-DHF did not produce significant cytotoxicity to A549 cells. Animal experiments showed that the combination of 7,8-DHF and vancomycin had a more significant therapeutic effect on S. aureus infection, reflecting the synergistic effect of 7,8-DHF with antibiotics. In conclusion, 7,8-DHF was able to target Hla to protect host cells from hemolysis while limiting the development of bacterial resistance.

The relationship of plasma fibrinogen with clinicopathological stages and tumor markers in patients with non-small cell lung cancer.

Numerous studies have shown that the blood of cancer patients are generally in hypercoagulable statement. The aim of the present research is to study the relationships of plasma fibrinogen (Fbg) levels with clinicopathological stages (CS) and tumor markers of non-small cell lung cancer (NSCLC).Baseline information, plasma Fbg levels, CS, and expression level of tumor markers were collected from medical records retrospectively. Unitary linear regression was used to analyze the relationships between continuous variables and Fbg, and multiple linear regression was used to analyze the relationships between categorical variables and Fbg. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (Version 4) for NSCLC were adopted to evaluate CS.A total of 652 NSCLC patients were included. Compared with the females, male patients had higher mean plasma Fbg levels (P < .001). The later the N stages (P = .002), M stages (P = .002), and CS (P = .001) were, the higher the average plasma Fbg levels were. The levels of squamous cell carcinoma antigen (P = .001), carbohydrate antigen 125 (P = .041), and neuron-specific enolase (P < .001) were positively correlated with plasma Fbg concentration. The plasma level of Fbg in lung adenocarcinoma patients (P < .001) was the lowest, while that of lung squamous cell carcinoma patients (P < .001) was the highest in NSCLC patients.The plasma Fbg concentration is related to gender, CS, and tumor markers in patients with NSCLC.