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- Uhlmann, J, et al.
(author)
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LL-37 Triggers Formation of Streptococcus pyogenes Extracellular Vesicle-Like Structures with Immune Stimulatory Properties
- 2016
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In: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 8:3, s. 243-257
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Journal article (peer-reviewed)abstract
- Reports have shown that the antimicrobial peptide LL-37 is abundantly expressed but has limited bactericidal effect in <i>Streptococcus pyogenes</i> infections. At sub-inhibitory concentrations, LL-37 has been reported to alter virulence gene expression. Here, we explored the interaction of <i>S. pyogenes</i> strains with LL-37, focusing on bacterial growth, cell surface alterations and pro-inflammatory responses. Bioscreen turbidity measurements of strain 5448 cultured in the presence or absence of LL-37 confirmed the poor antimicrobial effect, and revealed a significant increase in turbidity of bacterial cultures exposed to sub-inhibitory concentrations of LL-37. However, this was not linked to increased bacterial counts. Electron microscopy of LL-37-exposed bacteria revealed the presence of vesicle-like structures on the bacterial surface. The vesicles stained positive for LL-37 and were released from the bacterial surface. Concentrated supernatants enriched in these structures had a broader protein content, including several virulence factors, compared to supernatants from untreated bacteria. The supernatants from LL-37-exposed bacteria were pro-inflammatory and elicited resistin and myeloperoxidase release from neutrophils. This is the first report on <i>S. pyogenes</i> extracellular vesicle-like structures formed at the bacterial surface in response to LL-37. The associated increased pro-inflammatory activity further implicates LL-37 as a potential factor involved in <i>S. pyogenes</i> pathogenesis.
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