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A lux-based Staphylococcus aureus bioluminescence screening assay for the detection/identification of antibiotics and prediction of antibiotic mechanisms

The Journal of Antibiotics volume 73, pages 828–836 (2020)Cite this article

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Abstract

The need for the discovery of new antibiotics and solving the antibiotic resistance problem requires rapid detection of antibiotics, identification of known antibiotics, and prediction of antibiotic mechanisms. The bacterial lux genes encode proteins that convert chemical energy into photonic energy and lead to bioluminescence. Exploiting this phenomenon, we constructed a lux-based bioluminescence system in Staphylococcus aureus by expressing lux genes under the control of stress-inducible chaperon promoters. When experiencing antibiotic stress, these constructed reporter strains showed clear bioluminescence response. Therefore, this bioluminescence screening system can be used for the detection of antibiotics in unknown chemical mixtures. Further analysis of bioluminescence response patterns showed that: (1) these bioluminescence response patterns are highly antibiotic specific and therefore can be used for rapid and cheap identification of antibiotics; and that (2) antibiotics having the same mechanism of action have similar bioluminescence patterns and therefore these patterns can be used for the prediction of mechanism for an unknown antibiotic with good sensitivity and specificity. With this bioluminescence screening assay, the discovery and analysis of new antibiotics can be promoted, which benefits in solving the antibiotic resistance problem.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China [Grant number 2017YFD0400301]; the National Natural Science Foundation of China [Grant numbers 31770042 and 31770043]; Shandong Province Key Research and Development Program [Grant numbers 2016GSF121040 and 2018GSF118008]; the Fundamental Research Funds of Shandong University [Grant numbers 2017JC028, 2018JC013, 2018JC027]; the State Key Laboratory of Microbial Technology Open Project Funds, Shandong University [Grant number M2018-07]; and Jinan Cultural Industry Development Fund. We would like to thank Prof. Julian Davies and Dr. Vivian Miao from University of British Columbia for kindly providing the pAmilux plasmid and good discussion on the work. We would like to thank Dr. Lili R. Mesak from University of British Columbia for helpful comments on our research strategy. We would also like to thank Dr. Haoxin Wang, Ms. Kun Zhang, Ms. Moli Sang, Ms. Yanan Ma, Ms. Wenya Su, Ms. Bianfang Wang, and Ms. Xin Wei from Shandong University for help during experiments. We would like to thank Mr. Xianbin Liu from the Core Facilities for Life and Environmental Sciences of Shandong University for assistance on bioluminescence detection.

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  1. These authors contributed equally: Zhongjun Yang, Qingyu Cui

Authors and Affiliations

  1. State Key Laboratory of Microbial Technology, Qilu Hospital, Shandong University, Qingdao, 266237, Shandong, China

    Zhongjun Yang, Qingyu Cui, Mengge Zhang, Mingyu Wang & Hai Xu

  2. Center for Optics Research and Engineering, Shandong University, Qingdao, 266237, Shandong, China

    Zhiqiang Li

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  1. Zhongjun Yang
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Correspondence to Mingyu Wang or Hai Xu.

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Yang, Z., Cui, Q., Zhang, M. et al. A lux-based Staphylococcus aureus bioluminescence screening assay for the detection/identification of antibiotics and prediction of antibiotic mechanisms. J Antibiot 73, 828–836 (2020). https://doi.org/10.1038/s41429-020-0349-7

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