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Updated: Jul 8, 2026

Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
Published on: February 23, 2014
A pneumococcal MerR-like regulator and S-nitrosoglutathione reductase are required for systemic virulence
Uwe H Stroeher1, Stephen P Kidd, Sian L Stafford
1Australian Bacterial Pathogenesis Program, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia.
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.
Insights
Streptococcus pneumoniae uses NmlR and AdhC to defend against nitric oxide (NO) stress. These factors are crucial for bacterial survival in the bloodstream during infection.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Streptococcus pneumoniae is a significant human pathogen.
- Nitric oxide (NO) is a key component of the host immune response.
- Bacterial defense mechanisms against NO are critical for pathogenesis.
Purpose of the Study:
- To identify and characterize novel components of the nitric oxide (NO) defense system in Streptococcus pneumoniae.
- To investigate the role of NmlR(sp) and AdhC in NO resistance and virulence.
Main Methods:
- Gene expression analysis (cotranscription of nmlR(sp) and adhC).
- Biochemical assays to measure NADH-GSNO oxidoreductase activity.
- In vitro susceptibility testing against NO.
- In vivo virulence studies using mouse models (nasopharyngeal adherence and intraperitoneal challenge).
Main Results:
- NmlR(sp) is a transcriptional regulator involved in NO defense.
- AdhC encodes an alcohol dehydrogenase with NADH-GSNO oxidoreductase activity.
- Mutants lacking nmlR(sp) or adhC showed increased susceptibility to NO and reduced oxidoreductase activity.
- NmlR(sp) and AdhC were essential for pneumococcal survival in the bloodstream but not for nasopharyngeal adherence.
Conclusions:
- NmlR(sp) and AdhC are novel components of a Streptococcus pneumoniae nitric oxide (NO) defense system.
- This NO defense system is critical for pneumococcal survival during systemic infection.
- These findings provide insights into bacterial pathogenesis and host-pathogen interactions.
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