Modulating Kinetics of the Amyloid-Like Aggregation of Phenol-Soluble Modulins by Changes in pH

The pathogen is recognized as one of the most frequent causes of biofilm-associated infections. The recently identified phenol-soluble modulin (PSM) peptides act as the key molecular effectors of staphylococcal biofilm maturation and promote the formation of an aggregated fibril structure. The aim of this study was to evaluate the effect of various pH values on the formation of functional amyloids of individual PSM peptides. Here, we combined a range of biophysical, chemical kinetics and microscopic techniques to address the structure and aggregation mechanism of individual PSMs under different conditions. We established that there is a pH-induced switch in PSM aggregation kinetics. Different lag times and growth of fibrils were observed, which indicates that there was no clear correlation between the rates of fibril elongation among different PSMs. This finding confirms that pH can modulate the aggregation properties of these peptides and suggest a deeper understanding of the formation of aggregates, which represents an important basis for strategies to interfere and might help in reducing the risk of biofilm-related infections.