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Updated: Nov 10, 2025
Experimental Human Pneumococcal Carriage
Published on: February 15, 2013
MetR is a molecular adaptor for pneumococcal carriage in the healthy upper airway
Chengwang Zhang1, Haoran An1,2, Jiao Hu1
1Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
Abstract:
Streptococcus pneumoniae resides in the human upper airway as a commensal but also causes pneumonia, bacteremia, meningitis, and otitis media. It remains unclear how pneumococci adapt to nutritional conditions of various host niches. We here show that MetR, a LysR family transcriptional regulator, serves as a molecular adaptor for pneumococcal fitness, particularly in the upper airway. The metR mutant of strain D39 rapidly disappeared from the nasopharynx but was marginally attenuated in the lungs and bloodstream of mice. RNA-seq and ChIP-seq analyses showed that MetR broadly regulates transcription of the genes involved in methionine synthesis and other functions under methionine starvation. Genetic and biochemical analyses confirmed that MetR is essential for the activation of methionine synthesis but not uptake. Co-infection of influenza virus partially restored the colonization defect of the metR mutant. These results strongly suggest that MetR is particularly evolved for pneumococcal carriage in the upper airway of healthy individuals where free methionine is severely limited, but it becomes dispensable where environmental methionine is relatively more abundant (e.g., inflamed upper airway and sterile sites). To the best of our knowledge, MetR represents the first known regulator particularly for pneumococcal carriage in healthy individuals.
Insights
MetR, a regulator, is crucial for Streptococcus pneumoniae survival in the upper airway by enabling methionine synthesis. This adaptation is vital for pneumococcal carriage in healthy individuals.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Streptococcus pneumoniae is a common human commensal and pathogen.
- Pneumococcal adaptation to diverse host niches remains poorly understood.
Purpose of the Study:
- To investigate the role of MetR, a LysR family transcriptional regulator, in pneumococcal fitness and adaptation.
- To elucidate MetR's function in regulating methionine synthesis and its impact on pneumococcal colonization.
Main Methods:
- RNA-sequencing (RNA-seq) and Chromatin immunoprecipitation sequencing (ChIP-seq) analyses.
- Genetic manipulation of Streptococcus pneumoniae strain D39 (metR mutant).
- In vivo mouse models for colonization studies (nasopharynx, lungs, bloodstream).
- Biochemical assays to assess methionine synthesis and uptake.
Main Results:
- A metR mutant showed significantly reduced colonization in the nasopharynx but not in the lungs or bloodstream.
- MetR was identified as a key regulator of methionine synthesis genes under methionine-limiting conditions.
- MetR is essential for activating methionine synthesis, not uptake.
- Influenza virus co-infection partially rescued the colonization defect of the metR mutant.
Conclusions:
- MetR is a critical molecular adaptor for Streptococcus pneumoniae fitness, particularly for carriage in the healthy upper airway.
- MetR's function is vital in environments with limited methionine, such as the healthy nasopharynx.
- MetR is dispensable in niches with higher methionine availability, like inflamed airways or sterile sites.
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