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https://doi.org/10.1111/cmi.12956
Title: | Streptolysin-induced endoplasmic reticulum stress promotes group A Streptococcal host-associated biofilm formation and necrotising fasciitis | Authors: | Vajjala, Anuradha Biswas, Debabrata Tay, Wei Hong Hanski, Emanuel Kline, Kimberly A |
Keywords: | Science & Technology Life Sciences & Biomedicine Cell Biology Microbiology UNFOLDED PROTEIN RESPONSE PROGRAMMED CELL-DEATH ER STRESS INDUCED APOPTOSIS IN-VIVO ACTIVATION VIRULENCE MODEL ATF6 PATHWAYS |
Issue Date: | 1-Jan-2019 | Publisher: | WILEY | Citation: | Vajjala, Anuradha, Biswas, Debabrata, Tay, Wei Hong, Hanski, Emanuel, Kline, Kimberly A (2019-01-01). Streptolysin-induced endoplasmic reticulum stress promotes group A Streptococcal host-associated biofilm formation and necrotising fasciitis. CELLULAR MICROBIOLOGY 21 (1). ScholarBank@NUS Repository. https://doi.org/10.1111/cmi.12956 | Abstract: | © 2018 John Wiley & Sons Ltd Group A Streptococcus (GAS) is a human pathogen that causes infections ranging from mild to fulminant and life-threatening. Biofilms have been implicated in acute GAS soft-tissue infections such as necrotising fasciitis (NF). However, most in vitro models used to study GAS biofilms have been designed to mimic chronic infections and insufficiently recapitulate in vivo conditions along with the host–pathogen interactions that might influence biofilm formation. Here, we establish and characterise an in vitro model of GAS biofilm development on mammalian cells that simulates microcolony formation observed in a mouse model of human NF. We show that on mammalian cells, GAS forms dense aggregates that display hallmark biofilm characteristics including a 3D architecture and enhanced tolerance to antibiotics. In contrast to abiotic-grown biofilms, host-associated biofilms require the expression of secreted GAS streptolysins O and S (SLO, SLS) that induce endoplasmic reticulum (ER) stress in the host. In an in vivo mouse model, the streptolysin null mutant is attenuated in both microcolony formation and bacterial spread, but pretreatment of soft-tissue with an ER stressor restores the ability of the mutant to form wild-type-like microcolonies that disseminate throughout the soft tissue. Taken together, we have identified a new role of streptolysin-driven ER stress in GAS biofilm formation and NF disease progression. | Source Title: | CELLULAR MICROBIOLOGY | URI: | https://scholarbank.nus.edu.sg/handle/10635/155503 | ISSN: | 14625814 14625822 |
DOI: | 10.1111/cmi.12956 |
Appears in Collections: | Staff Publications Elements |
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