Background: Biofilm-related infections are difficult to be treated because of higher resistance to antimicrobial agents. Current study aims to characterize the influence of zinc oxide nanoparticles (ZnO-NPs) on bothS. aureussusceptibility to antibiotics and pathogenesis.Methods: The influence of ZnO-NPs on biofilm formation byS. aureuswas characterized by the crystal violet and tube assay. The synergistic effect of ZnO-NPs in combination with antibiotics onS. aureuswas characterized using the checkerboard method. The effect of ZnO-NPs onS. aureuscell surface hydrophobicity and blood hemolysis was investigated. RT-qPCR was used to investigate the effect of ZnO-NPs on the expression of biofilm related genes (icaA, icaRandsarA),katAandsigB. The impact of ZnO-NPs onS. aureuspathogenesis was evaluated using mice infection model.Results: ZnO-NPs exhibited a good antibiofilm activity againstS. aureus. The findings indicate a synergistic antibiofilm effect of combination between ZnO-NPs and tested antibiotics. ZnO-NPs were capable of decreasingS. aureuscell surface hydrophobicity which could account for observed decrease in bacterial biofilm forming capacity. Moreover, ZnO-NPs-treated bacteria exhibited a significant decrease in blood hemolysis relative to control untreatedS. aureus. The expression of biofilm related genes was significantly repressed in ZnO-NPs treated bacteria as compared to untreated cells. Finally, the effect of ZnO-NPs onS. aureuspathogenesis was investigated using mice infection model where ZnO-NPs accelerated healing of wounds in mice as compared to control untreated mice.Conclusions: Present data support the efficiency of ZnO-NPs as antibiofilm agent in treatment ofS. aureusinfections. This study recommends the incorporation of ZnO-NPs as adjuvant with other antibiotics targetingS. aureusbased on the promising findings obtained herein in order to control infection with this pathogen.

Salmonella enterica is a common cause of many enteric infections worldwide and is successfully engineered to deliver heterologous antigens to be used as vaccines. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) RNA-guided Cas9 endonuclease is a promising genome editing tool. In the current study, a CRISPR-Cas9 system was used to target S.enterica sdiA that encodes signal molecule receptor SdiA and responds to the quorum sensing (QS) signaling compounds N-acylhomoserine lactones (AHLs). For this purpose, sdiA was targeted in both S.enterica wild type (WT) and the ΔssaV mutant strain, where SsaV has been reported to be an essential component of SPI2-T3SS. The impact of sdiA mutation on S. enterica virulence was evaluated at both early invasion and later intracellular replication in both the presence and absence of AHL. Additionally, the influence of sdiA mutation on the pathogenesis S. enterica WT and mutants was investigated in vivo, using mice infection model. Finally, the minimum inhibitory concentrations (MICs) of various antibiotics against S. enterica strains were determined. Present findings show that mutation in sdiA significantly affects S.enterica biofilm formation, cell adhesion and invasion. However, sdiA mutation did not affect bacterial intracellular survival. Moreover, in vivo bacterial pathogenesis was markedly lowered in S.enterica ΔsdiA in comparison with the wild-type strain. Significantly, double-mutant sdiA and ssaV attenuated the S. enterica virulence and in vivo pathogenesis. Moreover, mutations in selected genes increased Salmonella susceptibility to tested antibiotics, as revealed by determining the MICs and MBICs of these antibiotics. Altogether, current results clearly highlight the importance of the CRISPR-Cas9 system as a bacterial genome editing tool and the valuable role of SdiA in S.enterica virulence. The present findings extend the understanding of virulence regulation and host pathogenesis of Salmonellaenterica.

Zinc oxide nanoparticles inhibits quorum sensing and virulence in Pseudomonas aeruginosa

Hepatitis C virus (HCV) is one of the most epidemic viral infections in the world. Three-quarters of individuals infected with HCV become chronic. As a consequence of persistent inflammation, a considerable percentage of chronic patients progress to liver fibrosis, cirrhosis, and finally hepatocellular carcinoma. Cytokines, which are particularly produced from T-helper cells, play a crucial role in immune protection against HCV and the progression of the disease as well. In this study, the role of interleukins IL-33, IL-17, and IL-25 in HCV patients and progression of disease from chronicity to hepatocellular carcinoma will be characterized in order to use them as biomarkers of disease progression. The serum levels of the tested interleukins were measured in patients suffering from chronic hepatitis C (CHC), hepatocellular carcinoma (HCC), and healthy controls (C), and their levels were correlated to the degree of liver fibrosis, liver fibrosis markers and viral load. In contrast to the IL-25 serum level, which increased in patients suffering from HCC only, the serum levels of both IL-33 and IL-17 increased significantly in those patients suffering from CHC and HCC. In addition, IL-33 serum level was found to increase by liver fibrosis progression and viral load, in contrast to both IL-17 and IL-25. Current results indicate a significant role of IL-33 in liver inflammation and fibrosis progress in CHC, whereas IL-17 and IL-25 may be used as biomarkers for the development of hepatocellular carcinoma.

Background: Pancreatic cancer is one of the most serious and lethal human cancers with a snowballing incidence around the world. The natural product celastrol has also been widely documented as a potent anti-inflammatory, anti-angiogenic, and anti-oxidant. Purpose: To elucidate the antitumor effect of celastrol on pancreatic cancer cells and its modulatory role on whole genome expression. Methods: The antitumor activity of celastrol on a panel of pancreatic cancer cells has been evaluated by Sulforhodamine B assay. Caspase 3/7 and histone-associated DNA fragments assays were done for apoptosis measurement. Additionally, prostaglandin (PGE2) inhibition was evaluated. Moreover, a microarray gene expression profiling was carried out to detect possible key players that modulate the antitumor effects of celastrol on cells of pancreatic cancer. Results: Our findings indicated that celastrol suppresses the cellular growth of pancreatic cancer cells, induces apoptosis, and inhibits PGE2 production. Celastrol modulated many signaling genes and its cytotoxic effect was mainly mediated via over-expression of ATF3 and DDIT3, and down-expression of RRM2 and MCM4. Conclusion: The current study aims to be a starting point to generate a hypothesis on the most significant regulatory genes and for a full dissection of the celastrol possible effects on each single gene to prevent the pancreatic cancer growth.

Current study aims to characterize the influence of sub-minimum inhibitory concentration (sub-MIC) of ciprofloxacin on Salmonella intracellular survival and host virulence. Herein, Salmonella resistance patterns to various antibiotics were in agreement with those reported in previous studies. Moreover, intracellular survival of both ciprofloxacin-sensitive and -resistant Salmonella was markedly reduced upon treatment with sub-MIC of ciprofloxacin as determined by gentamicin protection assay. These findings were further confirmed using immunostaining indicating an inhibitory effect of sub-MIC of ciprofloxacin on Salmonella intracellular survival. RT-qPCR revealed that expression of genes encoding Salmonella type three secretion system (TTSS) decreased upon bacterial exposure to sub-MIC of ciprofloxacin. Furthermore, bacterial exposure to sub-MIC of ciprofloxacin significantly reduced expression of both sifA and sifB, which are important for Salmonella filaments formation within the host. Treatment of Salmonella with sub-MIC of ciprofloxacin reduced bacterial capacity to kill mice infection models. A lower mortality rate was observed in mice injected with Salmonella treated with sub-MIC of ciprofloxacin as compared with mice inoculated with untreated bacteria. Collectively, current findings indicate that, in addition to its bactericidal potential, sub-MIC of ciprofloxacin could inhibit Salmonella intracellular survival, virulence genes expression as well as host pathogenesis, providing another mechanism for ciprofloxacin in limiting Salmonella host infection.