Abstract
The opportunistic pathogen Staphylococcus aureus is recognized as one of the most frequent causes of biofilm-associated infections. The recently discovered phenol soluble modulins (PSMs) are small α-helical amphipathic peptides that act as the main molecular effectors of staphylococcal biofilm maturation, promoting the formation of an extracellular fibril structure with amyloid-like properties. Here, we combine computational, biophysical and in cell analysis to address the specific contribution of individual PSMs to biofilm structure. We demonstrate that despite their highly similar sequence and structure, contrary to what it was previously thought, not all PSMs participate in amyloid fibril formation. A balance of hydrophobic/hydrophilic forces and helical propensity seems to define the aggregation propensity of PSMs and control their assembly and function. This knowledge would allow to target specifically the amyloid properties of these peptides. In this way, we show that Epigallocatechin-3-gallate (EGCG), the principal polyphenol in green tea, prevents the assembly of amyloidogenic PSMs and disentangles their preformed amyloid fibrils.
Highlights
Methicillin-resistant Staphylococcus aureus (MRSA) strains are involved in hospital acquired “nosocomial” infections such as endocarditis, necrotizing pneumonia and septic shock upon clinical infection[1,2,3,4]
The genes of S. aureus phenol soluble modulins (PSMs) peptides are encoded in its core genome and, they are produced by virtually all strains: four are expressed from the alpha operon (α-psm1–4), two are expressed from the beta operon (β-psm1–2), and the delta hemolysin (δ-toxin) is encoded in the regulatory RNA, RNAIII18
We analyzed the S. aureus PSMs amyloid formation mechanism in order to dissect the specific contribution of these short peptides to the biofilm structure and how this relates to intracellular toxicity
Summary
Methicillin-resistant Staphylococcus aureus (MRSA) strains are involved in hospital acquired “nosocomial” infections such as endocarditis, necrotizing pneumonia and septic shock upon clinical infection[1,2,3,4]. These data confirm the previously described PSMs ability to form amyloid structures[15] indicating, that this property is only attributable to α-PSM1 and α-PSM4 peptides, which contribute to amyloid formation with distinct aggregation propensities.
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