Streptolysin-induced endoplasmic reticulum stress promotes Group A Streptococcal host-associated biofilm formation and necrotising fasciitis

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 designe...

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Main Authors: Vajjala, Anuradha, Biswas, Debabrata, Tay, Wei Hong, Hanski, Emanuel, Kline, Kimberly Ann
Other Authors: School of Biological Sciences
Format: Journal Article
Language:English
Published: 2019
Subjects:
Online Access:https://hdl.handle.net/10356/104884
http://hdl.handle.net/10220/48125
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author Vajjala, Anuradha
Biswas, Debabrata
Tay, Wei Hong
Hanski, Emanuel
Kline, Kimberly Ann
author2 School of Biological Sciences
author_facet School of Biological Sciences
Vajjala, Anuradha
Biswas, Debabrata
Tay, Wei Hong
Hanski, Emanuel
Kline, Kimberly Ann
author_sort Vajjala, Anuradha
collection NTU
description 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.
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spelling ntu-10356/1048842020-09-21T11:34:31Z Streptolysin-induced endoplasmic reticulum stress promotes Group A Streptococcal host-associated biofilm formation and necrotising fasciitis Vajjala, Anuradha Biswas, Debabrata Tay, Wei Hong Hanski, Emanuel Kline, Kimberly Ann School of Biological Sciences Cellular and Molecular Mechanisms of Inflammation, Campus for Research Excellence and Technological Enterprise (CREATE) Department of Microbiology and Immunology, National University of Singapore (NUS)-The Hebrew University of Jerusalem (HUJ), Singapore. Singapore Centre for Environmental Life Sciences and Engineering Biofilms ER Stress DRNTU::Science::Biological sciences 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. NRF (Natl Research Foundation, S’pore) NMRC (Natl Medical Research Council, S’pore) Accepted version 2019-05-08T09:02:25Z 2019-12-06T21:41:57Z 2019-05-08T09:02:25Z 2019-12-06T21:41:57Z 2018 Journal Article Vajjala, A., Biswas, D., Tay, W. H., Hanski, E., & Kline, K. A. (2018). Streptolysin‐induced endoplasmic reticulum stress promotes Group A Streptococcal host‐associated biofilm formation and necrotising fasciitis. Cellular Microbiology, 21(1), e12956-. doi:10.1111/cmi.12956 1462-5814 https://hdl.handle.net/10356/104884 http://hdl.handle.net/10220/48125 10.1111/cmi.12956 en Cellular Microbiology © 2018 John Wiley & Sons Ltd. All rights reserved. This paper was published in Cellular Microbiology and is made available with permission of John Wiley & Sons Ltd. 16 p. application/pdf
spellingShingle Biofilms
ER Stress
DRNTU::Science::Biological sciences
Vajjala, Anuradha
Biswas, Debabrata
Tay, Wei Hong
Hanski, Emanuel
Kline, Kimberly Ann
Streptolysin-induced endoplasmic reticulum stress promotes Group A Streptococcal host-associated biofilm formation and necrotising fasciitis
title Streptolysin-induced endoplasmic reticulum stress promotes Group A Streptococcal host-associated biofilm formation and necrotising fasciitis
title_full Streptolysin-induced endoplasmic reticulum stress promotes Group A Streptococcal host-associated biofilm formation and necrotising fasciitis
title_fullStr Streptolysin-induced endoplasmic reticulum stress promotes Group A Streptococcal host-associated biofilm formation and necrotising fasciitis
title_full_unstemmed Streptolysin-induced endoplasmic reticulum stress promotes Group A Streptococcal host-associated biofilm formation and necrotising fasciitis
title_short Streptolysin-induced endoplasmic reticulum stress promotes Group A Streptococcal host-associated biofilm formation and necrotising fasciitis
title_sort streptolysin induced endoplasmic reticulum stress promotes group a streptococcal host associated biofilm formation and necrotising fasciitis
topic Biofilms
ER Stress
DRNTU::Science::Biological sciences
url https://hdl.handle.net/10356/104884
http://hdl.handle.net/10220/48125
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AT hanskiemanuel streptolysininducedendoplasmicreticulumstresspromotesgroupastreptococcalhostassociatedbiofilmformationandnecrotisingfasciitis
AT klinekimberlyann streptolysininducedendoplasmicreticulumstresspromotesgroupastreptococcalhostassociatedbiofilmformationandnecrotisingfasciitis