Coevolution between marine Aeromonas and phages reveals temporal trade-off patterns of phage resistance and host population fitness.

Coevolution of bacteria and phages is an important host and parasite dynamic in marine ecosystems, contributing to the understanding of bacterial community diversity. On the time scale, questions remain concerning what is the difference between phage resistance patterns in marine bacteria and how advantageous mutations gradually accumulate during coevolution. In this study, marine Aeromonas was co-cultured with its phage for 180 days and their genetic and phenotypic dynamics were measured every 30 days. We identified 11 phage resistance genes and classified them into three categories: lipopolysaccharide (LPS), outer membrane protein (OMP), and two-component system (TCS). LPS shortening and OMP mutations are two distinct modes of complete phage resistance, while TCS mutants mediate incomplete resistance by repressing the transcription of phage genes. The co-mutation of LPS and OMP was a major mode for bacterial resistance at a low cost. The mutations led to significant reductions in the growth and virulence of bacterial populations during the first 60 days of coevolution, with subsequent leveling off. Our findings reveal the marine bacterial community dynamics and evolutionary trade-offs of phage resistance during coevolution, thus granting further understanding of the interaction of marine microbes.

Design combinations of evolved phage and antibiotic for antibacterial guided by analyzing the phage resistance of poorly antimicrobial phage.

Although antibiotics are the primary method against bacterial infections, the rapid emergence of antibiotic resistance has forced interest in alternative antimicrobial strategies. Phage has been considered a new biological antimicrobial agent due to its high effectiveness in treating bacterial infections. However, the applications of phage therapy have been limited by the quick development of phage-resistant bacteria. Therefore, more effective phage treatment strategies need to be explored guided by characterizing phage-resistant mutants. In this study, Pseudomonas plecoglossicida phage vB_PpS_SYP was isolated from the sewage but exhibited weak antibacterial activity caused by phage-resistant bacteria. Phage-resistant mutants were isolated and their whole genomes were analyzed for differences. The results showed that mutations in glycosyltransferase family 1 (GT-1) and hypothetical outer membrane protein (homP) led to bacterial phage resistance. The GT-1 mutants had lower biofilm biomass and higher antibiotic sensitivity than wild-type strain. Phage SYP evolved a broader host range and improved antimicrobial efficacy to infect homP mutants. Therefore, we designed a strategy for combined antibiotic and evolved phage inhibition driven by the two phage-resistant mutants. The results showed that the combination was more effective against bacteria than either antibiotics or phage alone. Our findings presented a novel approach to utilizing poorly antimicrobial phages by characterizing their phage-resistant mutants, with the potential to be expanded to include phage therapy for a variety of pathogens. IMPORTANCE The rapid emergence of antibiotic resistance renews interest in phage therapy. However, the lack of efficient phages against bacteria and the emergence of phage resistance impaired the efficiency of phage therapy. In this study, the isolated Pseudomonas plecoglossicida phage exhibited poor antibacterial capacity and was not available for phage therapy. Analysis of phage-resistant mutants guided the design of antibacterial strategies for the combination of antibiotics with evolved phages. The combination has a good antibacterial effect compared to the original phage. Our findings facilitate ideas for the development of antimicrobial-incapable phage, which have the potential to be applied to the phage treatment of other pathogens.

Shenling Baizhu San improves functional dyspepsia in rats as revealed by 1H-NMR based metabolomics.

Functional dyspepsia (FD), a common gastrointestinal disorder around the world, is driven by multiple factors, making prevention and treatment a major challenge. Shenling Baizhu San (SBS), a classical prescription of traditional Chinese medicine, has been proven to be effective in gastrointestinal disorders. However, studies on SBS improving FD are few. Thus, our study aimed to evaluate the effect of SBS on FD and further to explore the mechanism underlying the interactions between FD and SBS by the metabolomics approach. A FD rat model was induced by multiple forms of mild stimulation, and proton nuclear magnetic resonance (1H-NMR) spectroscopy and multivariate data analysis were used to profile the fecal and urinary metabolome in the FD rats during SBS intervention. Significant dyspeptic symptoms such as weight loss, poor appetite, reduced gastrointestinal motility and decreased absorptive capacity were observed in the FD rats, which were subsequently improved by SBS. Additionally, the levels of citrate, branched chain acids and pyruvate decreased, and the levels of choline, trimethylamine and taurine increased in the FD rats. Furthermore, the metabolic disorders were amended with SBS intervention mainly by modulating the metabolic pathways involved in energy metabolism, amino acid metabolism, and gut microbiota and host co-metabolism. Overall, our study highlighted the effect of SBS on the disturbed metabolic pathways in the FD rats, providing new insight into the mechanism of SBS treatment for FD from the perspective of metabolomics.

Berberine ameliorates colonic damage accompanied with the modulation of dysfunctional bacteria and functions in ulcerative colitis rats.

Intestinal flora imbalance is one of the potential pathogenesis of inflammatory bowel diseases, and the study aims to discover the effect of berberine on the composition and function of gut microbiota in ulcerative colitis (UC) rats. UC rats were induced by dextran sulfate sodium (DSS) and administrated with berberine. Colonic morphological changes and claudin-1 protein of colon tissues were primarily examined to validate the protective effects brought by berberine treatment. Then the composition and function of gut microbiota were analyzed, accompanied with quantitative analysis of serum amino acids. The results showed that berberine could not only ameliorate the colonic damages in DSS-induced UC rats but also regulate the gut microbiota by increasing lactic acid-producing bacteria and carbohydrate hydrolysis bacteria as well as decreasing conditional pathogenic bacteria. Accordingly, the relevant functions of above bacteria were improved, including the metabolism and biosynthesis of amino acids, capability of DNA replication and repair, carbohydrate digestion and absorption and glycolysis/gluconeogenesis. Furthermore, the serum amino acids were regulated and showed high correlation with the gut microbiota after berberine treatment. In conclusion, the study confirms the effect of berberine on ameliorating the colonic damage and highlights some specific bacteria and relevant functions linked with berberine treatment, exploring the potential of gut microbiota as a diagnostic biomarker or a therapeutic target in UC treatment.

[Chemical constituents of Myripnois dioica].

To study the chemical constituents of the aerial parts of Myripnois dioica. Twelve compounds were separated from the 95% ethanol extract of M. dioica by using various chromatographic techniques. Their stuctures were identified on the basis of their physicochemical properties and spectral data as 8-desoxyurospermal A(1), zaluzanin C(2), dehydrozaluzanin C(3), glucozaluzanin C(4), macrocliniside B(5), macrocliniside I(6), taraxinic acid-14-O-ß-D-glucopyranoside(7), ainsliaside B(8), apigenin(9), luteolin(10), apigenin-7-O-ß-D-glucopyranoside(11), and luteolin-7-O-ß-D-glucopyranoside(12). Except for compound 8, the other compounds were isolated from this genus for the first time. Compound 8 was found to decrease blood glucose level properly in alloxan-induced diabetic mice.