title: The stringent response controls catalases in Pseudomonas aeruginosa and is required for hydrogen peroxide and antibiotic tolerance.
abstract: Pseudomonas aeruginosa, a human opportunistic pathogen, possesses a number of antioxidant defense enzymes under the control of multiple regulatory systems. We recently reported that inactivation of the P. aeruginosa stringent response (SR), a starvation stress response controlled by the alarmone (p)ppGpp, caused impaired antioxidant defenses and antibiotic tolerance. Since catalases are key antioxidant enzymes in P. aeruginosa, we compared the levels of H2O2 susceptibility and catalase activity in P. aeruginosa wild-type and ΔrelA ΔspoT (ΔSR) mutant cells. We found that the SR was required for optimal catalase activity and mediated H2O2 tolerance during both planktonic and biofilm growth. Upon amino acid starvation, induction of the SR upregulated catalase activity. Full expression of katA and katB also required the SR, and this regulation occurred through both RpoS-independent and RpoS-dependent mechanisms. Furthermore, overexpression of katA was sufficient to restore H2O2 tolerance and to partially rescue the antibiotic tolerance of ΔSR cells. All together, these results suggest that the SR regulates catalases and that this is an important mechanism in protecting nutrient-starved and biofilm bacteria from H2O2- and antibiotic-mediated killing.
authors: Department of Microbiology and Immunology, McGill University, Quebec, Canada.
authors: Malika
authors: M
authors: Khakimova
authors: Heather G
authors: HG
authors: Ahlgren
authors: Joe J
authors: JJ
authors: Harrison
authors: Ann M
authors: AM
authors: English
authors: Dao
authors: D
authors: Nguyen
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006861:Hydrogen Peroxide / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; D006861:Hydrogen Peroxide; D002374:Catalase