Open AccessA Pneumococcal MerR‐Like Regulator andS‐nitrosoglutathione Reductase Are Required for Systemic Virulence
Author(s) -
Uwe H. Stroeher,
Stephen P. Kidd,
Sian Stafford,
Michael P. Jennings,
James C. Paton,
Alastair G. McEwan
Publication year - 2007
Publication title -
the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1086/523107
Subject(s) - virulence , microbiology and biotechnology , streptococcus pneumoniae , mutant , reductase , biology , nitric oxide , regulator , superoxide , gene , biochemistry , enzyme , antibiotics , endocrinology
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.
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