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AdcAII of Streptococcus pneumoniae Affects Pneumococcal Invasiveness
Lindsey R Brown1, Steven M Gunnell1, Adam N Cassella1
1Department of Biological Sciences, Mississippi State University, Mississippi State, MS, 39762, United States of America.
Abstract:
Across bacterial species, metal binding proteins can serve functions in pathogenesis in addition to regulating metal homeostasis. We have compared and contrasted the activities of zinc (Zn2+)-binding lipoproteins AdcA and AdcAII in the Streptococcus pneumoniae TIGR4 background. Exposure to Zn2+-limiting conditions resulted in delayed growth in a strain lacking AdcAII (ΔAdcAII) when compared to wild type bacteria or a mutant lacking AdcA (ΔAdcA). AdcAII failed to interact with the extracellular matrix protein laminin despite homology to laminin-binding proteins of related streptococci. Deletion of AdcA or AdcAII led to significantly increased invasion of A549 human lung epithelial cells and a trend toward increased invasion in vivo. Loss of AdcAII, but not AdcA, was shown to negatively impact early colonization of the nasopharynx. Our findings suggest that expression of AdcAII affects invasiveness of S. pneumoniae in response to available Zn2+ concentrations.
Insights
Streptococcus pneumoniae uses zinc-binding lipoproteins AdcA and AdcAII for growth and invasion. Loss of AdcAII impairs growth in low zinc conditions and nasopharyngeal colonization, while both lipoproteins affect bacterial invasion.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Metal-binding proteins play crucial roles in bacterial pathogenesis and homeostasis.
- Streptococcus pneumoniae utilizes zinc (Zn2+) for various functions.
- Lipoproteins AdcA and AdcAII are zinc-binding proteins in S. pneumoniae.
Purpose of the Study:
- To compare and contrast the activities of zinc-binding lipoproteins AdcA and AdcAII in Streptococcus pneumoniae.
- To investigate the roles of AdcA and AdcAII in bacterial growth, invasion, and colonization.
Main Methods:
- Comparative analysis of wild type, ΔAdcA, and ΔAdcAII Streptococcus pneumoniae strains.
- Assessment of bacterial growth under zinc-limiting conditions.
- Evaluation of bacterial interaction with host cells (A549 lung epithelial cells) and in vivo models.
Main Results:
- Deletion of AdcAII (ΔAdcAII) resulted in delayed growth under zinc-limiting conditions.
- AdcAII did not interact with laminin, unlike homologous proteins.
- Deletion of AdcA or AdcAII significantly increased invasion of A549 cells and showed a trend toward increased in vivo invasion.
- Loss of AdcAII, but not AdcA, negatively impacted early nasopharyngeal colonization.
Conclusions:
- AdcAII is important for S. pneumoniae growth under zinc-limiting conditions.
- Both AdcA and AdcAII contribute to bacterial invasion, with AdcAII's role being influenced by zinc availability.
- AdcAII plays a significant role in early nasopharyngeal colonization.
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