title: A pneumococcal MerR-like regulator and S-nitrosoglutathione reductase are required for systemic virulence.
abstract: A transcriptional regulator, NmlR(sp), has been identified in Streptococcus pneumoniae that is required for defense against nitric oxide (NO) stress. The nmlR(sp) gene is cotranscribed with adhC, which encodes an alcohol dehydrogenase that is able to reduce S-nitrosoglutathione (GSNO) with NADH as reductant. nmlR(sp) and adhC mutants exhibited a reduced level of NADH-GSNO oxidoreductase activity and were more susceptible to killing by NO than were wild-type cells. Comparison of the virulence of wild-type and mutant strains by use of a mouse model system showed that NmlR(sp) and AdhC do not play a key role in the adherence of pneumococci to the nasopharynx in vivo. An intraperitoneal challenge experiment revealed that both NmlR(sp) and AdhC were required for survival in blood. These data identify novel components of a NO defense system in pneumococci that are required for systemic infection.
authors.affiliation: Australian Bacterial Pathogenesis Program, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia.
authors.forename: Uwe H
authors.initials: UH
authors.lastname: Stroeher
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Kidd
authors.forename: Sian L
authors.initials: SL
authors.lastname: Stafford
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jennings
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.forename: Alastair G
authors.initials: AG
authors.lastname: McEwan
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D009305:Nasopharynx / Q000382:microbiology; D009344:Neisseria gonorrhoeae / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism; D010802:Phylogeny; D020545:Respiratory Mucosa / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C051124:MerR protein, Bacteria; D009243:NAD; D009569:Nitric Oxide; C020145:formaldehyde dehydrogenase (glutathione); D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent