Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria

Dao Nguyen, Amruta Joshi-Datar, Francois Lepine, Elizabeth Bauerle, Oyebode Olakanmi, Karlyn Beer, Geoffrey McKay, Richard Siehnel, James Schafhauser, Yun Wang, Bradley E Britigan, Pradeep K. Singh

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Abstract

Bacteria become highly tolerant to antibiotics when nutrients are limited. The inactivity of antibiotic targets caused by starvation-induced growth arrest is thought to be a key mechanism producing tolerance. Here we show that the antibiotic tolerance of nutrient-limited and biofilm Pseudomonas aeruginosa is mediated by active responses to starvation, rather than by the passive effects of growth arrest. The protective mechanism is controlled by the starvation-signaling stringent response (SR), and our experiments link SR-mediated tolerance to reduced levels of oxidant stress in bacterial cells. Furthermore, inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics and markedly enhanced the efficacy of antibiotic treatment in experimental infections.

Original languageEnglish (US)
Pages (from-to)982-986
Number of pages5
JournalScience
Volume334
Issue number6058
DOIs
StatePublished - Nov 18 2011

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Nguyen, D., Joshi-Datar, A., Lepine, F., Bauerle, E., Olakanmi, O., Beer, K., McKay, G., Siehnel, R., Schafhauser, J., Wang, Y., Britigan, B. E., & Singh, P. K. (2011). Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science, 334(6058), 982-986. https://doi.org/10.1126/science.1211037