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Bacterial and host factors affecting acquisition of Streptococcus pneumoniae in a murine model
Daniel P Fecko1, Cindy Wu1, Jeffrey N Weiser1
1Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA.
Abstract:
Initial acquisition is a critical step in the establishment of colonization that in turn enables transmission to new hosts and potentially leads to invasive disease. Here, we studied host and bacterial factors affecting acquisition, as distinct from those affecting colonization density, using Streptococcus pneumoniae (Spn) in a mouse model. Acquisition was quantified using nasal inocula of limiting size to determine the proportion of hosts infected, as well as the median infectious dose. Infant mice (<7 days of age) were highly susceptible to acquisition (ID50 < 30 CFU) compared with adults (>6 weeks of age), with rates declining with increasing host age. Prior influenza A infection greatly increased acquisition in adults. Expression of Spn capsule was also an important factor influencing acquisition in adults, with less of a role for the highly susceptible infants. Prior Spn colonization with a heterologous or homologous strain effectively blocked acquisition in infants by completely occupying the upper respiratory tract niche. Nasal microbiota and immunity due to prior colonization were not found to be factors limiting acquisition. Together, our findings show how high carriage rates of encapsulated Spn during early life and in the setting of recent viral infection could be explained by effects on acquisition. Our study describes an approach for studying factors that specifically affect the step of acquisition.
Insights
Young mice are highly susceptible to Streptococcus pneumoniae (Spn) acquisition, which is increased by influenza A infection in adults. Prior Spn colonization blocks acquisition in infants by occupying the nasal niche.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Initial acquisition of bacteria is crucial for host colonization, transmission, and potential disease.
- Understanding factors influencing bacterial acquisition is key to controlling infectious diseases.
Purpose of the Study:
- To investigate host and bacterial factors specifically affecting Streptococcus pneumoniae (Spn) acquisition, separate from colonization density.
- To elucidate mechanisms behind high Spn carriage rates in early life and after viral infections.
Main Methods:
- Utilized a mouse model to quantify Spn acquisition using limiting nasal inocula and determining median infectious dose (ID50).
- Compared acquisition rates in infant versus adult mice, and in the presence/absence of prior influenza A infection.
- Assessed the impact of Spn capsule expression and prior Spn colonization on acquisition.
Main Results:
- Infant mice (<7 days) were highly susceptible to Spn acquisition (ID50 < 30 CFU) compared to adults (>6 weeks).
- Prior influenza A infection significantly increased Spn acquisition in adult mice.
- Spn capsule expression influenced acquisition in adults, while prior Spn colonization effectively blocked acquisition in infants.
Conclusions:
- Host age and prior viral infection significantly impact Spn acquisition.
- Bacterial factors like capsule expression and colonization niche occupancy play critical roles in acquisition.
- Findings explain high Spn carriage rates in specific host conditions and highlight acquisition as a key regulatory step.
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