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Published on: November 16, 2016
Strain-Dependent Effect of Capsule on Transmission and Persistence in an Infant Mouse Model of Group A Streptococcus
Luis Alberto Vega1, Misu A Sanson1, Brittany J Shah1
1Division of Infectious Diseases, Department of Pediatrics, McGovern Medical School, University of Texas Health Sciences Center at Houston, Houston, Texas, USA.
Insights
Group A Streptococcus (GAS) transmission and persistence were studied in an infant mouse model. Capsule production impacts GAS shedding and persistence, but strain background is critical for these effects.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Group A Streptococcus (GAS) is a significant human pathogen causing various diseases.
- Asymptomatic pharyngeal carriage of GAS serves as a reservoir for transmission.
- Investigating GAS transmission mechanisms is challenging due to limitations in human and non-primate models.
Purpose of the Study:
- To adapt an infant mouse model for studying GAS transmission and persistence.
- To investigate the role of capsule production in GAS transmission and persistence.
- To determine if strain background influences the effect of capsule on GAS transmission and persistence.
Main Methods:
- Adaptation of an infant mouse model for pneumococcal colonization and transmission.
- Evaluation of GAS burden and transmission rates in the mouse model.
- Comparison of transmission and persistence between capsule-positive (emm3) and capsule-negative (emm87) GAS strains.
Main Results:
- The infant mouse model recapitulated the human correlation between GAS burden and transmission.
- Capsule production was linked to increased GAS shedding, irrespective of strain.
- Restoring capsule in emm87 did not enhance transmissibility, and capsule absence enhanced persistence only in the emm87 background.
Conclusions:
- Strain background significantly modulates the impact of capsule on GAS transmission and persistence.
- Factors beyond capsule are necessary for the transmission of capsule-negative emm types.
- The infant mouse model provides a valuable tool for studying GAS pathogenesis and transmission dynamics.
Abstract:
Streptococcus pyogenes (group A Streptococcus [GAS]) is a human pathogen responsible for a wide range of diseases. Asymptomatic carriage of GAS in the human pharynx is commonplace and a potential reservoir for GAS transmission. Early studies showed that GAS transmission correlated with high bacterial burdens during the acute symptomatic phase of the disease. Human studies and the nonhuman primate model are generally impractical for investigation of the bacterial mechanisms contributing to GAS transmission and persistence. To address this gap, we adapted an infant mouse model of pneumococcal colonization and transmission to investigate factors that influence GAS transmission and persistence. The model recapitulated the direct correlation between GAS burden and transmission during the acute phase of infection observed in humans and nonhuman primates. Furthermore, our results indicate that the ratio of colonized to uncolonized hosts influences the rates of GAS transmission and persistence. We used the model to test the hypothesis that capsule production influences GAS transmission and persistence in a strain-dependent manner. We detected significant differences in rates of transmission and persistence between capsule-positive (emm3) and capsule-negative (emm87) GAS strains. Capsule was associated with higher levels of GAS shedding, independent of the strain background. In contrast to the capsule-positive emm3 strain, restoring capsule production in emm87 GAS did not increase transmissibility, and the absence of capsule enhanced persistence only in the capsule-negative (emm87) strain background. These data suggest that strain background (capsule positive versus capsule negative) influences the effect of capsule in GAS transmission and persistence and that as-yet-undefined factors are required for the transmission of capsule-negative emm types.
