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Organotypic Tissue Model Systems for Investigating Host-Pathogen Interactions In Vitro
Published on: March 28, 2025
Capsule expression in Streptococcus mitis modulates interaction with oral keratinocytes and alters susceptibility to
H V Rukke1, S A Engen1, K Schenck1
1Department of Oral Biology, Faculty of Dentistry, University of Oslo, Norway.
Abstract:
Streptococcus mitis is a colonizer of the oral cavity and the nasopharynx, and is closely related to Streptococcus pneumoniae. Both species occur in encapsulated and unencapsulated forms, but in S. mitis the role of the capsule in host interactions is mostly unknown. Therefore, the aim of this study was to examine how capsule expression in S. mitis can modulate interactions with the host with relevance for colonization. The S. mitis type strain, as well as two mutants of the type strain, an isogenic capsule deletion mutant, and a capsule switch mutant expressing the serotype 4 capsule of S. pneumoniae TIGR4, were used. Wild-type and capsule deletion strains of S. pneumoniae TIGR4 were included for comparison. We found that capsule production in S. mitis reduced adhesion to oral and lung epithelial cells. Further, exposure of oral epithelial cells to encapsulated S. mitis resulted in higher interleukin-6 and CXCL-8 transcription levels relative to the unencapsulated mutant. Capsule expression in S. mitis increased the sensitivity to human neutrophil peptide 1-3 but reduced the sensitivity to human β-defensin-3 and cathelicidin. This was in contrast with S. pneumoniae in which capsule expression has been generally associated with increased sensitivity to human antimicrobial peptides (AMPs). Collectively, these findings indicate that capsule expression in S. mitis is important in modulating interactions with epithelial cells, and is associated with increased or reduced susceptibility to AMPs depending on the nature of the AMP.
Insights
Capsule production in Streptococcus mitis affects how it interacts with host cells and defenses. Encapsulated S. mitis shows reduced adhesion and altered susceptibility to antimicrobial peptides.
Area of Science:
- Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Streptococcus mitis colonizes the oral cavity and nasopharynx, closely related to Streptococcus pneumoniae.
- The role of the capsule in S. mitis host interactions is largely unknown.
- Capsules are known virulence factors in related bacteria like S. pneumoniae.
Purpose of the Study:
- To investigate how capsule expression in S. mitis modulates host interactions relevant to colonization.
- To compare the effects of capsule expression in S. mitis versus S. pneumoniae.
Main Methods:
- Utilized S. mitis type strain, capsule deletion mutant, and capsule switch mutant.
- Included wild-type and capsule deletion S. pneumoniae TIGR4 for comparison.
- Assessed bacterial adhesion to epithelial cells and cytokine/chemokine transcription (IL-6, CXCL-8).
- Evaluated susceptibility to human antimicrobial peptides (AMPs): HNP1-3, HBD-3, and cathelicidin.
Main Results:
- Capsule production in S. mitis reduced adhesion to oral and lung epithelial cells.
- Encapsulated S. mitis induced higher IL-6 and CXCL-8 transcription in oral epithelial cells compared to the unencapsulated mutant.
- Capsule expression altered S. mitis susceptibility to AMPs: increased sensitivity to HNP1-3, but decreased sensitivity to HBD-3 and cathelicidin.
- This AMP sensitivity profile contrasts with S. pneumoniae, where capsules typically increase AMP sensitivity.
Conclusions:
- Capsule expression in S. mitis plays a significant role in modulating host cell interactions.
- The S. mitis capsule influences susceptibility to AMPs in a manner dependent on the specific peptide.
- These findings highlight distinct capsule functions in S. mitis compared to S. pneumoniae regarding host defense evasion.
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