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Tabachnikov, O.

Publications and source records attributed to Tabachnikov, O..

2 recordsLinked to original sources

Resilience and Charge-Dependent Fibrillation of Functional Amyloids: Interactions of Pseudomonas Biofilm-Associated FapB and FapC

FapC and FapB are biofilm-associated amyloids involved in the virulence of Pseudomonas and other bacteria. We herein demonstrate their exceptional thermal and chemical resilience, suggesting that biofilm structures might withstand standard sterilization, thereby contributing to the persistence of P. aeruginosa infections. Our findings also underscore the impact of environmental factors on Fap proteins, suggesting that orthologs in different Pseudomonas strains adapt to specific environments and roles. Challenging previous assumptions about a simple nucleation role for FapB in promoting FapC aggregation, the study shows a significant influence of FapC on FapB aggregation. The interaction between FapB and FapC is intricate: FapB stabilizes FapC fibrils, while FapC slows down FapB fibrillation but can still serve as a cross-seeding template. This complex interplay is key to understanding their roles in bacterial biofilms. Furthermore, the study highlights distinct differences between Fap and E. colis curli CsgA amyloid, where CsgB assumes a simple unidirectional role in nucleating CsgA fibrillation, emphasizing the importance of a comprehensive understanding of various amyloid systems. This knowledge is vital for developing effective intervention strategies against bacterial infections and leveraging the unique properties of these amyloids in technological applications such as novel bio-nanomaterials or protective coatings.

biochemistry↗

Toxic Determinants of Staphylococcus aureus PSMα3 Cross-α Amyloid

The phenol-soluble modulin (PSM) peptide family, secreted by Staphylococcus aureus, performs various virulence activities, some mediated by the formation of amyloid fibrils of diverse architectures. Specifically, PSM1 and PSM4 structure the S. aureus biofilm by assembling into robust cross-{beta} amyloid fibrils. PSM3, the most cytotoxic member of the family, assembles into cross- fibrils in which -helices stack into tightly mated sheets, mimicking the cross-{beta} architecture. Here we demonstrated that massive T-cell deformation and death is linked with PSM3 aggregation and co-localization with cell membranes. Our extensive mutagenesis analyses supported the role of positive charges, and especially Lys17, in interactions with the membrane, and suggested their regulation by inter- and intra-helical electrostatic interactions within the cross- fibril. We hypothesize that PSM3 cytotoxicity is governed by the ability to form cross- fibrils and involves a dynamic process of co-aggregation with cell membrane, rupturing it. HighlightsO_LIThe cytotoxic S. aureus PSM3 assembles into cross- fibrils C_LIO_LICross- fibril polymorphism and mutations-induced secondary structure switching C_LIO_LIRegulation by cross- fibril inter- and intra-helical electrostatic interactions C_LIO_LIToxicity as a putative dynamic process of PSM3 co-aggregation with membranes C_LI

biochemistry↗