The BR domain of PsrP interacts with extracellular DNA to promote bacterial aggregation; structural insights into pneumococcal biofilm formation

Abstract : The major human pathogen Streptococcus pneumoniae is a leading cause of disease and death worldwide. Pneumococcal biofilm formation within the nasopharynx leads to long-term colonization and persistence within the host. We have previously demonstrated that the capsular surface-associated pneumococcal serine rich repeat protein (PsrP), key factor for biofilm formation, binds to keratin-10 (KRT10) through its microbial surface component recognizing adhesive matrix molecule (MSCRAMM)-related globular binding region domain (BR187-385). Here, we show that BR187-385 also binds to DNA, as demonstrated by electrophoretic mobility shift assays and size exclusion chromatography. Further, heterologous expression of BR187-378 or the longer BR120-378 construct on the surface of a Gram-positive model host bacterium resulted in the formation of cellular aggregates that was significantly enhanced in the presence of DNA. Crystal structure analyses revealed the formation of BR187-385 homo-dimers via an intermolecular β-sheet, resulting in a positively charged concave surface, shaped to accommodate the acidic helical DNA structure. Furthermore, small angle X-ray scattering and circular dichroism studies indicate that the aggregate-enhancing N-terminal region of BR120-166 adopts an extended, non-globular structure. Altogether, our results suggest that PsrP adheres to extracellular DNA in the biofilm matrix and thus promotes pneumococcal biofilm formation.
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Article dans une revue
Scientific Reports, Nature Publishing Group, 2016, 6, pp.32371. 〈10.1038/srep32371〉
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http://hal.univ-grenoble-alpes.fr/hal-01406377
Contributeur : Frank Thomas <>
Soumis le : jeudi 1 décembre 2016 - 10:24:20
Dernière modification le : jeudi 11 janvier 2018 - 06:15:24

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Tim Schulte, Cecilia Mikaelsson, Audrey Beaussart, Alexey Kikhney, Maya Deshmukh, et al.. The BR domain of PsrP interacts with extracellular DNA to promote bacterial aggregation; structural insights into pneumococcal biofilm formation. Scientific Reports, Nature Publishing Group, 2016, 6, pp.32371. 〈10.1038/srep32371〉. 〈hal-01406377〉

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