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Optical control of antibacterial activity

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Abstract

Bacterial resistance is a major problem in the modern world, stemming in part from the build-up of antibiotics in the environment. Novel molecular approaches that enable an externally triggered increase in antibiotic activity with high spatiotemporal resolution and auto-inactivation are highly desirable. Here we report a responsive, broad-spectrum, antibacterial agent that can be temporally activated with light, whereupon it auto-inactivates on the scale of hours. The use of such a ‘smart’ antibiotic might prevent the build-up of active antimicrobial material in the environment. Reversible optical control over active drug concentration enables us to obtain pharmacodynamic information. Precisely localized control of activity is achieved, allowing the growth of bacteria to be confined to defined patterns, which has potential for the development of treatments that avoid interference with the endogenous microbial population in other parts of the organism. 

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Figure 1: Control of bacterial growth with a photoswitchable antibacterial agent.
Figure 2: Auto-inactivation of antibiotic activity.
Figure 3: Pharmacodynamic study with photoswitchable quinolone shows that antibacterial effect is exhibited in the exponential phase.
Figure 4: Bacterial patterning with light.

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Acknowledgements

This work was supported financially by the Netherlands Organization for Scientific Research (NWO-CW), The Royal Netherlands Academy of Arts and Sciences (KNAW), the European Research Council (ERC; advanced grant no. 227897 to B.L.F.) and the Ministry of Education, Culture and Science (Gravity programme no. 024.001.035). The authors thank C. Poloni for help with the bacterial patterning experiments and W.R. Browne for discussions.

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Contributions

B.L.F., W.A.V. and W.S. conceived the project and wrote the manuscript. W.A.V. designed the molecules. W.A.V. and M.J.H. performed the synthesis. W.A.V. and J.P.B. performed bacterial growth studies. B.L.F., W.S. and A.J.M.D. guided the research. All authors discussed the results and implications and commented on the manuscript at all stages.

Corresponding author

Correspondence to Ben L. Feringa.

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The authors declare no competing financial interests.

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Velema, W., van der Berg, J., Hansen, M. et al. Optical control of antibacterial activity. Nature Chem 5, 924–928 (2013). https://doi.org/10.1038/nchem.1750

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