4.5 Article

Actinomycin D: a novel Pseudomonasaeruginosa quorum sensing inhibitor from the endophyte Streptomycescyaneochromogenes RC1

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SPRINGER
DOI: 10.1007/s11274-022-03360-y

关键词

Actinomycin D; Biofilm; Pseudomonas aeruginosa; Quorum sensing; Virulence factor

资金

  1. National Natural Science Foundation of China [82160664]
  2. Natural Science Foundation of Hainan Province [221CXTD434, 221QN170]

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Actinomycin D has been found to have good activity against Pseudomonas aeruginosa infection and can inhibit the bacteria's quorum sensing system. It not only reduces the production of multiple virulence factors but also loosens and flattens the bacterial biofilm structure.
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 mu g/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.

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