Transcriptomic and Metabolomic Analysis Revealed Multifaceted Effects of Phage Protein Gp70.1 on Pseudomonas aeruginosa.

The impact of phage infection on the host cell is severe. In order to take over the cellular machinery, some phage proteins were produced to shut off the host biosynthesis early in the phage infection. The discovery and identification of these phage-derived inhibitors have a significant prospect of application in antibacterial treatment. This work presented a phage protein, gp70.1, with non-specific inhibitory effects on Pseudomonas aeruginosa and Escherichia coli. Gp70.1 was encoded by early gene - orf 70.1 from P. aeruginosa phage PaP3. The P. aeruginosa with a plasmid encoding gp70.1 showed with delayed growth and had the appearance of a small colony. The combination of multifaceted analysis including microarray-based transcriptomic analysis, RT-qPCR, nuclear magnetic resonance (NMR) spectroscopy-based metabolomics and phenotype experiments were performed to investigate the effects of gp70.1 on P. aeruginosa. A total of 178 genes of P. aeruginosa mainly involved in extracellular function and metabolism were differentially expressed in the presence of gp70.1 at three examined time points. Furthermore, our results indicated that gp70.1 had an extensive impact on the extracellular phenotype of P. aeruginosa, such as motility, pyocyanin, extracellular protease, polysaccharide, and cellulase. For the metabolism of P. aeruginosa, the main effect of gp70.1 was the reduction of amino acid consumption. Finally, the RNA polymerase sigma factor RpoS was identified as a potential cellular target of gp70.1. Gp70.1 was the first bacterial inhibitor identified from Pseudomonas aeruginosa phage PaP3. It was also the first phage protein that interacted with the global regulator RpoS of bacteria. Our results indicated the potential value of gp70.1 in antibacterial applications. This study preliminarily revealed the biological function of gp70.1 and provided a reference for the study of other phage genes sharing similarities with orf70.1.

Global Transcriptomic Analysis of Interactions between Pseudomonas aeruginosa and Bacteriophage PaP3.

The interactions between Bacteriophage (phage) and host bacteria are widespread in nature and influences of phage replication on the host cells are complex and extensive. Here, we investigate genome-wide interactions of Pseudomonas aeruginosa (P. aeruginosa) and its temperate phage PaP3 at five time points during phage infection. Compared to the uninfected host, 38% (2160/5633) genes of phage-infected host were identified as differentially expressed genes (DEGs). Functional analysis of the repressed DEGs revealed infection-stage-dependent pathway communications. Based on gene co-expression analysis, most PaP3 middle genes were predicted to have negative impact on host transcriptional regulators. Sub-network enrichment analysis revealed that adjacent genes of PaP3 interacted with the same host genes and might possess similar functions. Finally, our results suggested that during the whole infection stage, the early genes of PaP3 had stronger regulatory role in host gene expression than middle and late genes, while the host genes involved amino acid metabolism were the most "vulnerable" targets of these phage genes. This work provides the basis for understanding survival mechanisms of parasites and host, and seeking phage gene products that could potentially be used in anti-bacterial infection.

Effect of black tea consumption on blood cholesterol: a meta-analysis of 15 randomized controlled trials.

BACKGROUND: The results of the studies that have investigated the effects of black tea on blood cholesterol are inconsistent. The aim of this study is to quantitatively assess the effects of black tea on cholesterol concentrations. METHODS: PubMed, Embase, MEDLINE, and Cochrane Library (through to July 2014) were searched for randomized controlled trials (RCTs) designed to investigate the effect of black tea on blood cholesterol concentrations. The study quality was assessed by the Jadad scoring criteria. Pooled effect of black tea consumption on blood cholesterol concentrations was evaluated by fixed-effects or random-effects model. Meta-regression analyses were conducted to estimate dose effects of black tea polyphenols on concentrations of blood cholesterol. Subgroup and sensitivity analyses were performed to assess the potential source of heterogeneity. RESULTS: The consumption of black tea did not significantly lower TC concentrations either in healthy subjects or patients with coronary artery diseases based on both fixed-effects and random-effects analysis. No significant change was observed in HDL-C concentrations in healthy participants or in subjects with coronary artery disease supplemented with black tea when compared with control participants. The pooled net change of LDL-C in healthy participants was -5.57 mg/dL (95% CI, -9.49 to -1.66 mg/dL; P = 0.005) in fixed-effects analysis and -4.56 (95% CI, -10.30 to 1.17 mg/dL; P = 0.12) in random-effects analysis. No significant net change was observed in LDL-C concentrations in patients with coronary artery disease. Subgroup and sensitivity did not significantly influence the overall outcomes of this meta-analysis. No significant dose effects of black tea polyphenols on blood cholesterol concentrations were detected in meta-regression analyses. CONCLUSION: The meta-analysis suggests that the consumption of black tea might not have beneficial effects on concentrations of TC, HDL-C, and LDL-C. Further high quality RCTs are needed to definitively draw a causal interpretation of the findings.