A pneumococcal MerR-like regulator and S-nitrosoglutathione reductase are required for systemic virulence

被引:42
作者
Stroeher, Uwe H. [1 ]
Kidd, Stephen P. [2 ]
Stafford, Sian L. [2 ]
Jennings, Michael P. [2 ]
Paton, James C. [1 ]
McEwan, Alastair G. [2 ]
机构
[1] Univ Adelaide, Sch Mol & Biomed Sci, Australian Bacterial Pathogenesis Program, Adelaide, SA, Australia
[2] Univ Queensland, Sch Mol & Microbial Sci, Ctr Metals Biol, Brisbane, Qld, Australia
基金
英国医学研究理事会;
关键词
D O I
10.1086/523107
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 NmlRsp 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.
引用
收藏
页码:1820 / 1826
页数:7
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