Staphylococcal Functional Amyloids: Structure, Pathogenic Roles, Biofilm Fortification, and Inhibition Strategies

Amyloid aggregates, which are hallmarks of various human diseases, show promising roles in almost all life forms. In the past few years, there has been a significant broadening of the diverse roles that bacterial functional amyloids play in nature, expanding the horizons of these fibrillar assemblies. Herein, we provide a review of the current understanding of staphylococcal functional amyloids, their multifaceted roles in pathogenesis, and strengthening biofilm-associated antibiotic resistance. This review aims to explore how staphylococcal biofilm strengthening amyloidogenic proteins and peptides, particularly derived from <i>Staphylococcus aureus</i> and <i>Staphylococcus epidermidis</i>, can act as dual-edged swords supporting pathogenesis in the planktonic stages and triggering infections in biofilms. We outline the different amyloid fibrillar species derived from these proteins/peptides and the molecules that have been discovered to target their amyloid transformation. This review also highlights how the noncanonical structural polymorphisms of these extracellular fibrillar amyloids are responsible for their functional diversity and discusses the techniques that are used recently for exploring staphylococcal amyloid structure assortment.