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Updated: Mar 31, 2026

Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
Dynamic niche-specific adaptations in Neisseria meningitidis during infection
Yan Liu1, Ding Zhang2, Åke Engström3
1School of Life Sciences, Inner Mongolia University for Nationalities, Tongliao 028000, China.
Abstract:
Neisseria meningitidis is an opportunistic human pathogen that usually colonizes the nasopharyngeal mucosa asymptomatically. Upon invasion into the blood and central nervous system, this bacterium triggers a fulminant inflammatory reaction with the manifestations of septicemia and meningitis, causing high morbidity and mortality. To reveal the bacterial adaptations to specific and dynamic host environments, we performed a comprehensive proteomic survey of N. meningitidis isolated from the nasal mucosa, CSF and blood of a mouse disease model. We could identify 51 proteins whose expression pattern has been changed during infection, many of which have not yet been characterized. The abundance of proteins was markedly lower in the bacteria isolated from the nasal mucosa compared to the bacteria from the blood and CSF, indicating that initiating adhesion is the harshest challenge for meningococci. The high abundance of the glutamate dehydrogenase (GdhA) and Opa1800 proteins in all bacterial isolates suggests their essential role in bacterial survival in vivo. To evaluate the biological relevance of our proteomic findings, four candidate proteins from representative functional groups, such as the bacterial chaperone GroEL, IMP dehydrogenase GuaB, and membrane proteins PilQ and NMC0101, were selected and their impact on bacterial fitness was investigated by mutagenesis assays. This study provides an integrated picture of bacterial niche-specific adaptations during consecutive infection processes.
Insights
This study reveals how Neisseria meningitidis adapts to different host environments during infection. Bacterial protein levels change significantly, with adhesion to the nasal mucosa being the most challenging step for survival.
Area of Science:
- Microbiology
- Pathogen Biology
- Proteomics
Background:
- Neisseria meningitidis is an opportunistic pathogen causing meningitis and septicemia.
- Bacterial adaptation to host environments is crucial for infection progression.
- Understanding these adaptations can inform therapeutic strategies.
Purpose of the Study:
- To comprehensively survey the proteome of N. meningitidis during infection.
- To identify bacterial proteins with altered expression in different host niches (nasal mucosa, blood, CSF).
- To investigate the functional roles of key proteins in bacterial fitness and survival in vivo.
Main Methods:
- Proteomic analysis of N. meningitidis isolated from various sites in a mouse model.
- Quantitative comparison of protein abundance across different infection stages.
- Mutagenesis assays to assess the impact of specific proteins on bacterial fitness.
Main Results:
- Identified 51 proteins with altered expression patterns during infection.
- Significantly lower protein abundance in nasal mucosa isolates compared to blood and CSF isolates, indicating adhesion challenges.
- High abundance of glutamate dehydrogenase (GdhA) and Opa1800 suggests essential roles in survival.
- Mutagenesis of GroEL, GuaB, PilQ, and NMC0101 provided insights into their functional relevance.
Conclusions:
- N. meningitidis exhibits significant niche-specific proteomic adaptations during infection.
- Bacterial adhesion to the nasal mucosa presents a major survival challenge.
- Specific proteins like GdhA and Opa1800 are critical for in vivo survival, and others play key roles in bacterial fitness.
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