Conserved molecular chaperone PrsA stimulates protective immunity against group A Streptococcus.

Group A Streptococcus (GAS) is a significant human pathogen that poses a global health concern. However, the development of a GAS vaccine has been challenging due to the multitude of diverse M-types and the risk of triggering cross-reactive immune responses. Our previous research has identified a critical role of PrsA1 and PrsA2, surface post-translational molecular chaperone proteins, in maintaining GAS proteome homeostasis and virulence traits. In this study, we aimed to further explore the potential of PrsA1 and PrsA2 as vaccine candidates for preventing GAS infection. We found that PrsA1 and PrsA2 are highly conserved among GAS isolates, demonstrating minimal amino acid variation. Antibodies specifically targeting PrsA1/A2 showed no cross-reactivity with human heart proteins and effectively enhanced neutrophil opsonophagocytic killing of various GAS serotypes. Additionally, passive transfer of PrsA1/A2-specific antibodies conferred protective immunity in infected mice. Compared to alum, immunization with CFA-adjuvanted PrsA1/A2 induced higher levels of Th1-associated IgG isotypes and complement activation and provided approximately 70% protection against invasive GAS challenge. These findings highlight the potential of PrsA1 and PrsA2 as universal vaccine candidates for the development of an effective GAS vaccine.

The Effect of Calycosin-7-O-ß-D-Glucoside and its Synergistic Augmentation of Cisplatin-induced Apoptosis in SK-OV-3 Cells.

OBJECTIVE: This study aims to examine the synergetic augmentation of calycosin-7-O-ß-D-glucoside (CG) on cisplatin (CDDP) to induce apoptosis of human epithelial ovarian SK-OV-3 cancer cells. METHODS: The SK-OV-3 cells were divided into four groups: control, CDDP monotherapy, CG monotherapy, and combined CDDP and CG treatment. The cell counting kit-8 method detected cell proliferation at different times and under different treatments. Hoechst 33258 staining and annexin V-FITC/propidium iodide double staining methods were used to observe the apoptosis of the SK-OV-3 cells. The caspase-3 enzyme activity detection method, quantitative reverse transcription-polymerase chain reaction, and western blot were used to detect the apoptosis-related factors and the activities of the enzyme in SK-OV-3 cells. RESULTS: The inhibition rates of SK-OV-3 cell proliferation when exposed to 10 µM of CDDP, 50 µM of CG, and a combination of 10 µM of CDDP and 50 µM of CG were 23.2% ± 1.1%, 26.7% ± 2.0%, and 46.7% ± 1.3% after 48 h, respectively. Following the use of the drug combination, the apoptosis rate and caspase-3 enzyme activity were significantly higher than in the single-drug treatment group; the data differences were also significant (p < 0.05). At the protein and ribonucleic acid levels, CG significantly enhanced the effect of CDDP on p53, caspase-3, caspase-9, Bax, and Bcl-2. CONCLUSION: In vitro, CG significantly increases the CDDP-induced apoptosis of the SK-OV-3 cells through the p53 pathway at the cellular level. In addition, using the drugs in combination reduces the toxicity and side effects caused by using CDDP alone.

Unique virulence role of post-translocational chaperone PrsA in shaping Streptococcus pyogenes secretome.

Streptococcus pyogenes (group A Streptococcus, GAS) is a strict human pathogen causing a broad spectrum of diseases and a variety of autoimmune sequelae. The pathogenesis of GAS infection mostly relies on the production of an extensive network of cell wall-associated and secreted virulence proteins, such as adhesins, toxins, and exoenzymes. PrsA, the only extracellular parvulin-type peptidyl-prolyl isomerase expressed ubiquitously in Gram-positive bacteria, has been suggested to assist the folding and maturation of newly exported proteins to acquire their native conformation and activity. Two PrsA proteins, PrsA1 and PrsA2, have been identified in GAS, but the respective contribution of each PrsA in GAS pathogenesis remains largely unknown. By combining comparative proteomic and phenotypic analysis approaches, we demonstrate that both PrsA isoforms are required to maintain GAS proteome homeostasis and virulence-associated traits in a unique and overlapping manner. The inactivation of both PrsA in GAS caused remarkable impairment in biofilm formation, host adherence, infection-induced cytotoxicity, and in vivo virulence in a murine soft tissue infection model. The concordance of proteomic and phenotypic data clearly features the essential role of PrsA in GAS full virulence.

[Exploration of developmental toxicity mechanism of pentachlorophenol using cDNA microarray].

0hpf zebrafish embryos were exposed to 50 microg/L pentachlorophenol(PCP) for 8h in vitro. Total RNA sample was extracted then and hybridized with Affymetrix Zebrafish Genome Array representing approximately 14 900 transcripts. A total of 1 149 transcripts was significantly up-regulated while 501 transcripts were down-regulated. Bioinformatic tools were used for further analysis. The result indicated that genes with significant expression changes were related to molecular functions including antioxidant activity, signal transducer activity, translation regulator activity, transcription regulator activity, et al. Genes regulated by BMP signals, FGF signals, and Nodal signals including smad2, smad5, bmp4, bmp7, flh, n-ras may involve in the developmental toxicity of PCP, with Signal log ratios of 4.6, 2.1, 1.6, 1.0, 1, 1.3, 1.0, respectively. This investigation may provide new biomarkers to further study of the developmental toxicity of PCP.