Actinomycin D: a novel Pseudomonas aeruginosa quorum sensing inhibitor from the endophyte Streptomyces cyaneochromogenes RC1.

The infections caused by Pseudomonas aeruginosa are difficult to treat due to its multidrug resistance. A promising strategy for controlling P. aeruginosa infection is targeting the quorum sensing (QS) system. Actinomycin D isolated from the metabolite of endophyte Streptomyces cyaneochromogenes RC1 exhibited good anti-QS activity against P. aeruginosa PAO1. Actinomycin D (50, 100, and 200 µg/mL) significantly inhibited the motility as well as reduced the production of multiple virulence factors including pyocyanin, protease, rhamnolipid, and siderophores. The images of confocal laser scanning microscopy and scanning electron microscopy revealed that the treatment of actinomycin D resulted in a looser and flatter biofilm structure. Real-time quantitative PCR analysis showed that the expression of QS-related genes lasI, rhlI, rhlR, pqsR, pslA, and pilA were downregulated dramatically. The production of QS signaling molecules N-(3-oxododecanoyl)-L-homoserine lactone and N-butanoyl-L-homoserine lactone were also decreased by actinomycin D. These findings suggest that actinomycin D, a potent in vitro anti-virulence agent, is a promising candidate to treat P. aeruginosa infection by interfering with the QS systems.

Characterization and chemical modification of PLN-1, an exopolysaccharide from Phomopsis liquidambari NJUSTb1.

Phomopsis liquidambari is a classical endophytic fungus with great application potential in ecology and agriculture; however, studies on its exopolysaccharides are lacking. Here, we aimed to evaluate the structure and bioactivity of PLN-1, an exopolysaccharide derived from the P. liquidambari NJUSTb1 strain. The structure was elucidated by chromatography/spectral methods and hydrolyzation. Immunomodulation, moisture absorption, and retention properties were investigated after sulfation and carboxymethylation modification. Results showed that PLN-1 contained a linear repeating unit of →[4)-α-d-Glcp-(1→6)-α-d-Glcp-(1→4)-α-d-Glcp-(1→4)-α-d-Glcp-(1→]n, with a molecular weight of 343 kDa. The degrees of substitution of sulfated polysaccharide (S-PLN-1) and carboxymethylated polysaccharide (C-PLN-1) were 1.228 and 0.903, respectively. S-PLN-1 showed stronger moisture absorption and retention properties than PLN (crude EPS), C-PLN1, and PLN-1. Furthermore, PLN, S-PLN-1, and C-PLN-1 stimulated the proliferation of RAW 264.7 cells with no cytotoxicity. The elucidation of PLN-1 in this study paves the way for future applications.