Open AccessInterplay of Pneumococcal Hydrogen Peroxide and Host-Derived Nitric Oxide
Author(s) -
Olaf Hoffmann,
Janine Zweigner,
Shan H. Smith,
Dorette Freyer,
Cordula Mahrhofer,
Emilie Dagand,
Elaine Tuomanen,
Joerg R. Weber
Publication year - 2006
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01932-05
Subject(s) - peroxynitrite , hydrogen peroxide , nitrotyrosine , nitric oxide , streptococcus pneumoniae , reactive oxygen species , reactive nitrogen species , microbiology and biotechnology , biology , bacteria , radical , superoxide , nitric oxide synthase , biochemistry , antibiotics , enzyme , genetics , endocrinology
Reactive oxygen and nitrogen species are released by immune-competent cells and contribute to cellular damage. On the other hand, certain pathogens, includingStreptococcus pneumoniae , are known to produce hydrogen peroxide (H2 O2 ), while production of nitrogen radicals by bacteria presumably occurs but has been poorly studied. We determined the relative contributions of bacterial versus host-derived oxygen and nitrogen radicals to cellular damage in pneumococcal infection. A special focus was placed on peroxynitrite as a hypothetical common product formed by the reaction of H2 O2 and NO. In microglial cultures, reduction of the formation of 3-nitrotyrosine and cellular damage required H2 O2 -deficient (ΔspxB or ΔcarB ) pneumococci and inhibition of host NO synthesis with aminoguanidine. In infected C57BL/6 mice, neuronal loss and immunopositivity for nitrotyrosine in the dentate gyrus were markedly reduced with ΔspxB or ΔcarB bacterial mutants and in inducible nitric oxide synthase knockout mice. We conclude that although host and bacteria both produce oxygen and nitrogen radicals, the interplay of prokaryotic H2 O2 and eukaryotic NO is a major contributor to cellular damage in pneumococcal meningitis.