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Identification of siderophores blocking infection of Pseudomonas aeruginosa from Kitasatospora sp. LS1784

The Journal of Antibiotics volume 77, pages 4–12 (2024)Cite this article

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Abstract

Siderophores are low-molecular-mass, high-affinity chelators of Fe3+ ions that are critical for the survival of bacteria in ferric deficient environment. Exogenous siderophores are potential bacteriostat by disrupting the iron-uptake process of pathogens. In our previous work to discover siderophores, strain LS1784 was previously predicted to produce new catecholate-type siderophores by genome analysis but no compounds were obtained. In this work, we reclassified train LS1784 as Kitasatospora sp. LS1784 according to the genome phylogenetic analysis. Then guided by CAS colorimetric assay and molecular network analysis, four catecholate-type siderophores were isolated from the ethyl acetate extract of LS1784 which were coincident with the initial prediction. Notably, compounds 2 and 3 were reported for the first time. Following activity screening, compound 3 showed sufficient anti-Pseudomonas aeruginosa-infection activity in Caenorhabditis elegans infection models, whereas all compounds exhibited no antimicrobial activity. These results indicated that compound 3 can enhance the survival of P. aeruginosa infecting C. elegans by reducing the virulence of P. aeruginosa rather than killing P. aeruginosa, which aligns with our previous findings. Moreover, these findings highlight the effectiveness of comprehensive approaches, including genome mining, CAS (Chromeazurol S) testing, and molecular network (MN) analysis, in identifying potential siderophores, thereby expanding the siderophores arsenal in bacteria for the development of anti-infective drugs.

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Acknowledgements

Dr. Jinwei Ren and Dr. Wenzhao Wang (State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences) are appreciated for their help in measuring the NMR and MS data. This work was supported in part by the National Natural Science Foundation of China grant 22277135 and 82073723.

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  1. These authors contributed equally: Baosong Chen, Yue Wang.

Authors and Affiliations

  1. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichenxi Road, Chaoyang District, Beijing, 100101, China

    Baosong Chen, Feng Xie, Hongwei Liu & Huanqin Dai

  2. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China

    Yue Wang & Hongwei Liu

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  1. Baosong Chen
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Correspondence to Hongwei Liu or Huanqin Dai.

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Chen, B., Wang, Y., Xie, F. et al. Identification of siderophores blocking infection of Pseudomonas aeruginosa from Kitasatospora sp. LS1784. J Antibiot 77, 4–12 (2024). https://doi.org/10.1038/s41429-023-00675-2

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