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Bacterial Factors Required for Transmission of Streptococcus pneumoniae in Mammalian Hosts
Hannah M Rowe1, Erik Karlsson1, Haley Echlin1
1Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USA.
Abstract:
The capacity of Streptococcus pneumoniae to successfully transmit and colonize new human hosts is a critical aspect of pneumococcal population biology and a prerequisite for invasive disease. However, the bacterial mechanisms underlying this process remain largely unknown. To identify bacterial factors required for transmission, we conducted a high-throughput genetic screen with a transposon sequencing (Tn-seq) library of a pneumococcal strain in a ferret transmission model. Key players in both metabolism and transcriptional regulation were identified as required for efficient bacterial transmission. Targeted deletion of the putative C3-degrading protease CppA, iron transporter PiaA, or competence regulatory histidine kinase ComD significantly decreased transmissibility in a mouse model, further validating the screen. Maternal vaccination with recombinant surface-exposed PiaA and CppA alone or in combination blocked transmission in offspring and were more effective than capsule-based vaccines. These data underscore the possibility of targeting pneumococcal transmission as a means of eliminating invasive disease in the population.
Insights
Identifying bacterial factors is key to understanding Streptococcus pneumoniae transmission. Targeting surface proteins like PiaA and CppA via maternal vaccination offers a promising strategy to block transmission and prevent invasive pneumococcal disease.
Area of Science:
- Microbiology
- Infectious Diseases
- Vaccinology
Background:
- Streptococcus pneumoniae transmission and colonization are crucial for disease but poorly understood.
- Bacterial mechanisms driving pneumococcal spread to new hosts remain largely unknown.
- Understanding these mechanisms is vital for controlling invasive pneumococcal disease.
Purpose of the Study:
- To identify bacterial factors essential for Streptococcus pneumoniae transmission.
- To evaluate novel vaccine strategies targeting transmission.
Main Methods:
- High-throughput genetic screening using transposon sequencing (Tn-seq) in a ferret model.
- Validation of identified genes (CppA, PiaA, ComD) through targeted deletion in a mouse model.
- Assessment of maternal vaccination efficacy using recombinant surface proteins (PiaA, CppA).
Main Results:
- Genetic screen identified key bacterial metabolism and transcriptional regulation factors for transmission.
- Deletion of CppA, PiaA, or ComD significantly reduced pneumococcal transmissibility.
- Maternal vaccination with recombinant PiaA and CppA effectively blocked offspring transmission, outperforming capsule-based vaccines.
Conclusions:
- Bacterial factors, including CppA and PiaA, are critical for Streptococcus pneumoniae transmission.
- Targeting pneumococcal transmission through maternal vaccination with surface proteins is a viable strategy.
- This approach holds potential for eliminating invasive pneumococcal disease.
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