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Engineering microbes for targeted strikes against human pathogens

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Abstract

Lack of pathogen specificity in antimicrobial therapy causes non-discriminant microbial cell killing that disrupts the microflora present. As a result, potentially helpful microbial cells are killed along with the pathogen, altering the biodiversity and dynamic interactions within the population. Moreover, the unwarranted exposure of antibiotics to microbes increases the likelihood of developing resistance and perpetuates the emergence of multidrug resistance. Synthetic biology offers an alternative solution where specificity can be conferred to reduce the non-specific, non-targeted activity of currently available antibiotics, and instead provides targeted therapy against specific pathogens and minimising collateral damage to the host’s inherent microbiota. With a greater understanding of the microbiome and the available genetic engineering tools for microbial cells, it is possible to devise antimicrobial strategies for novel antimicrobial therapy that are able to precisely and selectively remove infectious pathogens. Herein, we review the strategies developed by unlocking some of the natural mechanisms used by the microbes and how these may be utilised in targeted antimicrobial therapy, with the promise of reducing the current global bane of multidrug antimicrobial resistance.

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Acknowledgements

This work was supported by the Summit Research Program of the National University Health System (NUHSRO/2016/053/SRP/05), the Synthetic Biology Initiative of the National University of Singapore (DPRT/943/09/14), the U.S. Defense Threat Reduction Agency (HDTRA1-13-0037) and the Ministry of Defence of Singapore (MINDEF, RE2016-074). We thank Dr. Ping Han for her comments on the manuscript.

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Authors and Affiliations

  1. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore, 117596, Singapore

    In Young Hwang, Hui Ling Lee, Wen Shan Yew & Matthew Wook Chang

  2. NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore

    In Young Hwang, Hui Ling Lee, James Guoxian Huang, Yvonne Yijuan Lim, Wen Shan Yew, Yung Seng Lee & Matthew Wook Chang

  3. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Rd, Singapore, 119074, Singapore

    James Guoxian Huang, Yvonne Yijuan Lim & Yung Seng Lee

  4. Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, 5 Lower Kent Ridge Rd, Singapore, 119074, Singapore

    James Guoxian Huang, Yvonne Yijuan Lim & Yung Seng Lee

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  1. In Young Hwang
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  2. Hui Ling Lee
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  6. Yung Seng Lee
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Correspondence to Matthew Wook Chang.

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Hwang, I.Y., Lee, H.L., Huang, J.G. et al. Engineering microbes for targeted strikes against human pathogens. Cell. Mol. Life Sci. 75, 2719–2733 (2018). https://doi.org/10.1007/s00018-018-2827-7

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  • DOI: https://doi.org/10.1007/s00018-018-2827-7

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