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

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Abstract

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.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This research was funded by National Natural Science Foundation of China (No. 82160664), Natural Science Foundation of Hainan Province (No. 221CXTD434 and No. 221QN170).

Funding

This work was supported by National Natural Science Foundation of China (Grant number [82160664]), Natural Science Foundation of Hainan Province (Grant numbers [221CXTD434] and [221QN170]).

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Contributions

All authors contributed to this study´s conception and design. Material preparation were performed by Y.Z., J.L. and Y.W.; data collection and analysis were performed by Y.Z., J.L., S.T. and D.W.; the figures were created by Y.Z., J.L., Y.W. and D.W.; the tables were made by S.T. and S.D.; the literature search was performed by Y.W. and S.T.; the framework of the manuscript was drafted by A.J.; the manuscript was written and revised Y.Z., J.L. and A.J. All authors reviewed the manuscript.

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Correspondence to Ai-Qun Jia.

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The manuscript does not contain experiments using animals and human studies.

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Zeng, YX., Liu, JS., Wang, YJ. et al. Actinomycin D: a novel Pseudomonas aeruginosa quorum sensing inhibitor from the endophyte Streptomyces cyaneochromogenes RC1. World J Microbiol Biotechnol 38, 170 (2022). https://doi.org/10.1007/s11274-022-03360-y

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  • DOI: https://doi.org/10.1007/s11274-022-03360-y

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