Abstract
The pathogen Staphylococcus aureus 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.
Highlights
A range of microbes are known to form biofilms by assembling into well-organized and complex communities on surfaces to endure different environments [1,2]
To investigate how different pH values alter the kinetic behavior of phenol-soluble modulin (PSM) peptides, monomers of all seven PSM peptides (PSMα1-4, PSMβ1-2, and δ-toxin) were incubated at a pH range from 1 to 12, and the aggregation kinetic was monitored using Thioflavin T (ThT)
At acidic pH from pH 1 to pH 4, PSMα1 forms fibrils within 10 to 40 h that have a significant ThT fluorescence signal and a half-time that decreases with increased pH values (Figure 1a)
Summary
A range of microbes are known to form biofilms by assembling into well-organized and complex communities on surfaces to endure different environments [1,2]. Biofilm formation proceeds from the initial contact of an individual microorganism with a surface. An extracellular polymeric substance (EPS) composed of proteins, polysaccharides, lipids, and/or extracellular DNA (eDNA) is produced, and a complex, three-dimensional structure is established to form a mature biofilm [3]. The EPS maintains the structural integrity of biofilms, protects microbes from high doses of antibiotics and harmful conditions such as oxidative stress, along with attacks by other organisms (e.g., host immune system) [4,5]. Aggregated proteins, in the form of functional bacterial amyloids, are key components of EPS, providing structural stability to biofilms [8,9]. The Salmonella Tafi protein, Pseudomonas fluorescens Fap proteins, E. coli curli, Bacillus subtilis TasA protein, and fungal hydrophobins are examples of such functional bacterial amyloids [10]
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