Dataset Information

Dissecting the contribution of Staphylococcus aureus ?-phenol-soluble modulins to biofilm amyloid structure.

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 ?-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.

SUBMITTER: Marinelli P

PROVIDER: S-EPMC5052566 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Dissecting the contribution of Staphylococcus aureus α-phenol-soluble modulins to biofilm amyloid structure.

Marinelli Patrizia P Pallares Irantzu I Navarro Susanna S Ventura Salvador S

Scientific reports 20161006

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 ...[more]

PMID: 27708403

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Project description:Incomplete killing of bacterial pathogens by antibiotics is an underlying cause of treatment failure and accompanying complications. Among those avoiding chemotherapy are persisters being individual cells in a population that for extended periods of time survive high antibiotic concentrations proposedly by being in a quiescent state refractory to antibiotic killing. While investigating the human pathogen Staphylococcus aureus and the influence of growth phase on persister formation, we noted that spent supernatants of stationary phase cultures of S. aureus or S. epidermidis, but not of distantly related bacteria, significantly reduced the persister cell frequency upon ciprofloxacin challenge when added to exponentially growing and stationary phase S. aureus cells. Curiously, the persister reducing activity of S. aureus supernatants was also effective against persisters formed by either S. carnosus or Listeria monocytogenes. The persister reducing component, which resisted heat but not proteases and was produced in the late growth phase in an agr quorum-sensing dependent manner, was identified to be the phenol-soluble modulin (PSM) toxins. S. aureus express several PSMs, each with distinct cytolytic and antimicrobial properties; however, the persister reducing activity was specifically linked to synthesis of the PSM? family. Correspondingly, a high-persister phenotype of a PSM? mutant was observed upon fluoroquinolone or aminoglycoside challenge, demonstrating that the persister reducing activity of PSMs can be endogenously synthesized or extrinsically added. Given that PSMs have been associated with lytic activity against bacterial membranes we propose that PSM toxins increase the susceptibility of persister cells to killing by intracellularly acting antibiotics and that chronic and re-occurring infections with quorum sensing, agr negative mutants may be difficult to treat with antibiotics because of persister cells formed in the absence of PSM toxins.

Dataset Information

Dissecting the contribution of Staphylococcus aureus ?-phenol-soluble modulins to biofilm amyloid structure.

Publications

Dissecting the contribution of Staphylococcus aureus α-phenol-soluble modulins to biofilm amyloid structure.

Similar Datasets

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