Staphylococcus aureus N-terminus formylated δ-toxin tends to form amyloid fibrils, while the deformylated δ-toxin tends to form functional oligomer complexes

Abstract

The community-associated Methicillin-resistant Staphylococcus aureus strain (CA-MRSA) is highly virulent and has become a major focus of public health professionals. Phenol-soluble modulins (PSM) are key factors in its increased virulence. δ-Toxin belongs to PSM family and has copious secretion in many S. aureus strains. In addition, δ-toxin exists in the S. aureus culture supernatant as both N-terminus formylated δ-toxin (fδ-toxin) and deformylated δ-toxin (dfδ-toxin) groups. Although δ-toxin has been studied for more than 70 years, its functions remain unclear. We isolated and purified PSMs from the supernatant of S. aureus MW2, and found fibrils and oligomers aggregates by Size Exclusion Chromatography. After analyzing PSM aggregates and using peptide simulations, we found that the difference in the monomer structure of fδ-toxin and dfδ-toxin might ultimately lead to differences in the aggregation ability: fδ-toxin and dfδ-toxin tend to form fibrils and oligomers respectively. Of note, we found that fδ-toxin fibrils enhanced the stability of biofilms, while dfδ-toxin oligomers promoted their dispersal. Additionally, oligomeric dfδ-toxin combined with PSMα to form a complex with enhanced functionality. Due to the different aggregation capabilities and functions of fδ-toxin and dfδ-toxin, we speculate that they may be involved in the regulation of physiological activities of S. aureus . Moreover, the dfδ-toxin oligomer not only provides a new form of complex in the study of PSMα, but also has significance as a reference in oligomer research pertaining to some human amyloid diseases.

Synergistic Antibacterial Activity with Conventional Antibiotics and Mechanism of Action of Shikonin against Methicillin-Resistant Staphylococcus aureus

“…This is the leading cause predisposing colonized individuals to subsequent surgical site infections [ 4 ]. As a major human causative agent, S. aureus usually colonizes the anterior nares of humans and causes a wide range of intractable infections, ranging from mild superficial skin and wound infections to fatal disseminated infections [ 5 , 6 ]. The most common affected sites are skin and soft tissues.…”

Phenol-Soluble Modulins From Staphylococcus aureus Biofilms Form Complexes With DNA to Drive Autoimmunity

“…We found that FSB stained the S. aureus SH1000 biofilm ( Figure 1A , left), while there was minimal visible FSB staining of the Δpsm mutant ( Figure 1A , right). This small amount of staining may be due to the presence of other amyloidogenic proteins in the S. aureus extracellular matrix, such as additional PSMs, which were not deleted in our Δpsm mutant and has been shown to form amyloid fibrils in vitro ( Zhou et al., 2021 ). Next S. aureus SH1000, its isogenic psm mutant, and UTI89, which expresses curli, were grown in sterile glass tubes and pellicles were stained by crystal violet.…”

Cell-Penetrating Antimicrobial Peptides Derived from an Atypical Staphylococcal δ-Toxin

“…To investigate structural determinants of STIP activity, we measured peptide secondary structures using circular dichroism (CD) spectroscopy. The S. aureus δ-toxin and other PSMs are known to form α-helices, higher order oligomers, and to possess an ability to form amyloid fibers ( 30 – 32 ). STIP3-1 and its variants appear unstructured in water and α-helical in 50% trifluoroethanol (TFE; vol/vol) whereas the S. auricularis δ-toxin was α-helical in both solvents ( Fig.…”