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

Dao Nguyen (1) , Amruta Joshi-Datar (2) , Francois Lepine (3) , Elizabeth Bauerle (2) , Oyebode Olakanmi (4) , Karlyn Beer (2) , Geoffrey Mckay (1) , Richard Siehnel (2) , James Schafhauser (1) , Yun Wang (5) , Bradley E Britigan (4, 6) , Pradeep K Singh (2)

1 Departments of Medicine, Microbiology and Immunology
2 Departments of Medicine and Microbiology
3 INRS-IAF - Institut Armand Frappier
4 Department of Internal Medicine
5 Department of Civil and Environmental Engineering [Evanston]
6 Veterans Administration

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.

Domains: Biotechnology; Biotechnology; Bacteriology

Dao Nguyen, Amruta Joshi-Datar, Francois Lepine, Elizabeth Bauerle, Oyebode Olakanmi, et al.. Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria.. Science, 2011, 334 (6058), pp.982-6. ⟨10.1126/science.1211037⟩. ⟨pasteur-00722468⟩