title: Effect of nonheme iron-containing ferritin Dpr in the stress response and virulence of pneumococci.
abstract: Streptococcus pneumoniae (pneumococcus) produces hydrogen peroxide as a by-product of metabolism and provides a competitive advantage against cocolonizing bacteria. As pneumococci do not produce catalase or an inducible regulator of hydrogen peroxide, the mechanism of resistance to hydrogen peroxide is unclear. A gene responsible for resistance to hydrogen peroxide and iron in other streptococci is that encoding nonheme iron-containing ferritin, dpr, but previous attempts to study this gene in pneumococcus by generating a dpr mutant were unsuccessful. In the current study, we found that dpr is in an operon with the downstream genes dhfr and clpX. We generated a dpr deletion mutant which displayed normal early-log-phase and mid-log-phase growth in bacteriologic medium but survived less well at stationary phase; the addition of catalase partially rescued the growth defect. We showed that the dpr mutant is significantly more sensitive to pH, heat, iron concentration, and oxidative stress due to hydrogen peroxide. Using a mouse model of colonization, we also showed that the dpr mutant displays a reduced ability to colonize and is more rapidly cleared from the nasopharynx. Our results thus suggest that Dpr is important for pneumococcal resistance to stress and for nasopharyngeal colonization.
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA Division of Infectious Disease, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Chun-Zhen
authors.initials: CZ
authors.lastname: Hua
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Howard
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Malley
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA yingjie.lu@childrens.harvard.edu.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Lu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D009154:Mutation / Q000235:genetics; D009876:Operon / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D011008:Pneumococcal Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics; D014774:Virulence / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D005293:Ferritins; D006861:Hydrogen Peroxide; D007501:Iron