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Wet-dry cycles protect surface-colonizing bacteria from major antibiotic classes

Abstract

Diverse antibiotic compounds are abundant in microbial habitats undergoing recurrent wet-dry cycles, such as soil, root and leaf surfaces, and the built environment. These antibiotics play a central role in microbial warfare and competition, thus affecting population dynamics and the composition of natural microbial communities. Yet, the impact of wet-dry cycles on bacterial response to antibiotics has been scarcely explored. Using the bacterium E. coli as a model organism, we show through a combination of experiments and computational modeling, that wet-dry cycles protect bacteria from beta-lactams. This is due to the combined effect of several mechanisms including tolerance induced by high salt concentrations and slow cell-growth, which are inherently associated with microscopic surface wetness—a hydration state typical to ‘dry’ periods. Moreover, we find evidence for a cross-protection effect, where lethal doses of antibiotic considerably increase bacterial survival during the dry periods. This work focuses on beta-lactams, yet similar protection was observed for additional major antibiotic classes. Our findings shed new light on how we understand bacterial response to antibiotics, with broad implications for population dynamics, interspecies interactions, and the evolution of antibiotic resistance in vast terrestrial microbial habitats.

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Fig. 1: Wet-dry cycles are prevalent in the largest terrestrial microbial habitats.
Fig. 2: Wet-dry cycles with MSW protect bacteria from beta-lactam antibiotics.
Fig. 3: Antibiotic deactivation in MSW and estimation of growth and lysis rates.
Fig. 4: Mathematical modeling provides a mechanistic understanding of antibiotic response under wet-dry cycles with MSW.
Fig. 5: Antibiotic responses of other strains to Amp.

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Acknowledgements

We thank Jonathan Friedman, Nathalie Balaban, Yael Helman, and Yitzhak Hadar for valuable comments and discussions. P. agglomerans 299R was kindly provided by Steve E. Lindow. NK is supported by research grants from the James S. McDonnell Foundation (Studying Complex Systems Scholar Award, Grant #220020475) and from the Israel Science Foundation (ISF #1396/19).

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YBM, MG, TO, and NK conceived the study. YBM and TO performed experiments. MG and TO performed image processing. MG and YBM performed data analyses. MG conducted mathematical modeling and simulations. All authors discussed the results and contributed to the final manuscript. NK supervised the project. YBM, MG, TO, and NK wrote the manuscript.

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Correspondence to Nadav Kashtan.

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Beizman-Magen, Y., Grinberg, M., Orevi, T. et al. Wet-dry cycles protect surface-colonizing bacteria from major antibiotic classes. ISME J 16, 91–100 (2022). https://doi.org/10.1038/s41396-021-01051-4

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