title: Overlapping and complementary oxidative stress defense mechanisms in nontypeable Haemophilus influenzae.
abstract: The Gram-negative commensal bacterium nontypeable Haemophilus influenzae (NTHI) can cause respiratory tract diseases that include otitis media, sinusitis, exacerbations of chronic obstructive pulmonary disease, and bronchitis. During colonization and infection, NTHI withstands oxidative stress generated by reactive oxygen species produced endogenously, by the host, and by other copathogens and flora. These reactive oxygen species include superoxide, hydrogen peroxide (H2O2), and hydroxyl radicals, whose killing is amplified by iron via the Fenton reaction. We previously identified genes that encode proteins with putative roles in protection of the NTHI isolate strain 86-028NP against oxidative stress. These include catalase (HktE), peroxiredoxin/glutaredoxin (PgdX), and a ferritin-like protein (Dps). Strains were generated with mutations in hktE, pgdX, and dps. The hktE mutant and a pgdX hktE double mutant were more sensitive than the parent to killing by H2O2. Conversely, the pgdX mutant was more resistant to H2O2 due to increased catalase activity. Supporting the role of killing via the Fenton reaction, binding of iron by Dps significantly mitigated the effect of H2O2-mediated killing. NTHI thus utilizes several effectors to resist oxidative stress, and regulation of free iron is critical to this protection. These mechanisms will be important for successful colonization and infection by this opportunistic human pathogen.
authors.affiliation: The Center for Microbial Pathogenesis at the Research Institute at Nationwide Children's Hospital and the Center for Microbial Interface Biology and Department of Pediatrics, The Ohio State University, Ohio, USA alistair.harrison@nationwidechildrens.org.
authors.forename: Alistair
authors.initials: A
authors.lastname: Harrison
authors.affiliation: The Center for Microbial Pathogenesis at the Research Institute at Nationwide Children's Hospital and the Center for Microbial Interface Biology and Department of Pediatrics, The Ohio State University, Ohio, USA.
authors.forename: Beth D
authors.initials: BD
authors.lastname: Baker
authors.affiliation: The Center for Microbial Pathogenesis at the Research Institute at Nationwide Children's Hospital and the Center for Microbial Interface Biology and Department of Pediatrics, The Ohio State University, Ohio, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Munson
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D006193:Haemophilus influenzae / Q000187:drug effects / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D016877:Oxidants; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase