Blowing epithelial cell bubbles with GumB: ShlA-family pore-forming toxins induce blebbing and rapid cellular death in corneal epithelial cells

• DOI: 10.1371/journal.ppat.1007825
• Publication Date: 2019-06-20T17:46:32Z
• Authors: Kimberly M. Brothers; Jake D. Callaghan; Nicholas A. Stella; Julianna M. Bachi...; Mohammed AlHigaylan; Kara L. Lehner; Jonathan M. Franks; Kira L. Lathrop; Elliot Collins; Deanna M. Schmitt; Joseph Horzempa; Robert M. Q. Shanks
• Keywords: 0301 basic medicine; Cell Death; QH301-705.5; Perforin; Swine; Type V Secretion Systems; Bacterial Toxins; Epithelium, Corneal; Epithelial Cells; RC581-607; Proteus; Serratia Infections; Mice; 03 medical and health sciences; RAW 264.7 Cells; Animals; Humans; Immunologic diseases. Allergy; Biology (General); Proteus Infections; Serratia marcescens; Research Article

Medical devices, such as contact lenses, bring bacteria in direct with human cells. Consequences of these host-pathogen interactions include the alteration mammalian cell surface architecture and induction cellular death that renders tissues more susceptible to infection. Gram-negative known induce blebbing by cells, Pseudomonas Vibrio species, do so through a type III secretion system-dependent mechanism. This study demonstrates subset from Enterobacteriaceae bacterial family membrane blebs variety types via V secretion-system dependent Here, we report ShlA-family cytolysins Proteus mirabilis Serratia marcescens were required blebbling death. Blebbing blocked an antioxidant RIP-1 MLKL inhibitors, implicating necroptosis observed phenotypes. Additional genetic studies determined IgaA stress-response protein, GumB, was necessary blebs. Data supported model where GumB shlBA are regulatory circuit Rcs stress response phosphorelay system for bleb formation pathogenesis invertebrate infection proliferation phagocytic line. introduces regulator S. common mechanism which elicit morphological changes on likely contributes damage corneal epithelial layer, enables access deeper parts tissue