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- Title
Blowing epithelial cell bubbles with GumB: ShlA-family pore-forming toxins induce blebbing and rapid cellular death in corneal epithelial cells.
- Authors
Brothers, Kimberly M.; Callaghan, Jake D.; Stella, Nicholas A.; Bachinsky, Julianna M.; AlHigaylan, Mohammed; Lehner, Kara L.; Franks, Jonathan M.; Lathrop, Kira L.; Collins, Elliot; Schmitt, Deanna M.; Horzempa, Joseph; Shanks, Robert M. Q.
- Abstract
Medical devices, such as contact lenses, bring bacteria in direct contact with human cells. Consequences of these host-pathogen interactions include the alteration of mammalian cell surface architecture and induction of cellular death that renders tissues more susceptible to infection. Gram-negative bacteria known to induce cellular blebbing by mammalian cells, Pseudomonas and Vibrio species, do so through a type III secretion system-dependent mechanism. This study demonstrates that a subset of bacteria from the Enterobacteriaceae bacterial family induce cellular death and membrane blebs in a variety of cell types via a type V secretion-system dependent mechanism. Here, we report that ShlA-family cytolysins from Proteus mirabilis and Serratia marcescens were required to induce membrane blebbling and cell death. Blebbing and cellular death were blocked by an antioxidant and RIP-1 and MLKL inhibitors, implicating necroptosis in the observed phenotypes. Additional genetic studies determined that an IgaA family stress-response protein, GumB, was necessary to induce blebs. Data supported a model where GumB and shlBA are in a regulatory circuit through the Rcs stress response phosphorelay system required for bleb formation and pathogenesis in an invertebrate model of infection and proliferation in a phagocytic cell line. This study introduces GumB as a regulator of S. marcescens host-pathogen interactions and demonstrates a common type V secretion system-dependent mechanism by which bacteria elicit surface morphological changes on mammalian cells. This type V secretion-system mechanism likely contributes bacterial damage to the corneal epithelial layer, and enables access to deeper parts of the tissue that are more susceptible to infection.
- Subjects
SECRETION; EPITHELIAL cells; SERRATIA marcescens; GRAM-negative bacteria; CELL death; CORNEA; BLEBS (Cytology); BACTERIAL proteins; TOXINS
- Publication
PLoS Pathogens, 2019, Vol 15, Issue 6, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1007825