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Characterization of Inflammatory Responses During Intranasal Colonization with Streptococcus pneumoniae
Published on: January 17, 2014
Phenotypic, genomic, and transcriptional characterization of Streptococcus pneumoniae interacting with human
Sheila Z Kimaro Mlacha1, Sandra Romero-Steiner, Julie C Dunning Hotopp
1Kenya Medical Research Institute, Wellcome Trust Research Programme, Kilifi, Kenya.
Insights
This study identifies novel bacterial factors influencing Streptococcus pneumoniae adherence to host cells. Understanding these adherence determinants is crucial for developing new strategies against pneumococcal disease.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Streptococcus pneumoniae causes significant global childhood illness and death.
- Existing pneumococcal vaccines are effective but do not prevent all disease.
- Identifying bacterial adherence factors is key to controlling pneumococcal infections.
Purpose of the Study:
- To identify novel factors involved in Streptococcus pneumoniae adherence to host cells.
- To compare adherence mechanisms between different pneumococcal strains.
- To understand the molecular basis of pneumococcal-host interactions.
Main Methods:
- Adherence assays and mutagenesis were employed.
- Functional genomics and electron microscopy were utilized.
- Comparative analysis of TIGR4 and G54 pneumococcal strains was performed.
Main Results:
- Bacterial adherence and invasion varied significantly between strains TIGR4 and G54.
- Upregulation of lic, psa, and phn operons was observed upon exposure to epithelial cells.
- Deletion of specific genes, including ∆SP_1922 within the pneumolysin operon, resulted in reduced bacterial adherence.
Conclusions:
- Novel potential determinants of pneumococcal adherence were identified.
- The study highlights strain-specific differences in adherence mechanisms.
- Findings contribute to understanding pneumococcal pathogenesis and vaccine development.
Background:
Streptococcus pneumoniae is a leading cause of childhood morbidity and mortality worldwide, despite the availability of effective pneumococcal vaccines. Understanding the molecular interactions between the bacterium and the host will contribute to the control and prevention of pneumococcal disease.
Results:
We used a combination of adherence assays, mutagenesis and functional genomics to identify novel factors involved in adherence. By contrasting these processes in two pneumococcal strains, TIGR4 and G54, we showed that adherence and invasion capacities vary markedly by strain. Electron microscopy showed more adherent bacteria in association with membranous pseudopodia in the TIGR4 strain. Operons for cell wall phosphorylcholine incorporation (lic), manganese transport (psa) and phosphate utilization (phn) were up-regulated in both strains on exposure to epithelial cells. Pneumolysin, pili, stress protection genes (adhC-czcD) and genes of the type II fatty acid synthesis pathway were highly expressed in the naturally more invasive strain, TIGR4. Deletion mutagenesis of five gene regions identified as regulated in this study revealed attenuation in adherence. Most strikingly, ∆SP_1922 which was predicted to contain a B-cell epitope and revealed significant attenuation in adherence, appeared to be expressed as a part of an operon that includes the gene encoding the cytoplasmic pore-forming toxin and vaccine candidate, pneumolysin.
Conclusion:
This work identifies a list of novel potential pneumococcal adherence determinants.
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