Type three secretion system-mediated escape of Burkholderia pseudomallei into the host cytosol is critical for the activation of NFκB

Boon Eng Teh; Christopher Todd French; Yahua Chen; Isabelle Gek Joo Chen; Ting Hsiang Wu; Enrico Sagullo; Pei Yu Chiou; Michael A. Teitell; Jeff F. Miller; Yunn Hwen Gan

doi:10.1186/1471-2180-14-115

Type three secretion system-mediated escape of Burkholderia pseudomallei into the host cytosol is critical for the activation of NFκB

Boon Eng Teh, Christopher Todd French, Yahua Chen, Isabelle Gek Joo Chen, Ting Hsiang Wu, Enrico Sagullo, Pei Yu Chiou, Michael A. Teitell, Jeff F. Miller, Yunn Hwen Gan

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Background: Burkholderia pseudomallei is the causative agent of melioidosis, a potentially fatal disease endemic in Southeast Asia and Northern Australia. This Gram-negative pathogen possesses numerous virulence factors including three "injection type" type three secretion systems (T3SSs). B. pseudomallei has been shown to activate NFκB in HEK293T cells in a Toll-like receptor and MyD88 independent manner that requires T3SS gene cluster 3 (T3SS3 or T3SS_Bsa). However, the mechanism of how T3SS3 contributes to NFκB activation is unknown. Results: Known T3SS3 effectors are not responsible for NFκB activation. Furthermore, T3SS3-null mutants are able to activate NFκB almost to the same extent as wildtype bacteria at late time points of infection, corresponding to delayed escape into the cytosol. NFκB activation also occurs when bacteria are delivered directly into the cytosol by photothermal nanoblade injection. Conclusions: T3SS3 does not directly activate NFκB but facilitates bacterial escape into the cytosol where the host is able to sense the presence of the pathogen through cytosolic sensors leading to NFκB activation.

Original language	English (US)
Article number	115
Journal	BMC microbiology
Volume	14
Issue number	1
DOIs	https://doi.org/10.1186/1471-2180-14-115
State	Published - May 6 2014
Externally published	Yes

ASJC Scopus subject areas

Microbiology
Microbiology (medical)

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@article{b2c2a007920e41318c98f94f2ea14f49,

title = "Type three secretion system-mediated escape of Burkholderia pseudomallei into the host cytosol is critical for the activation of NFκB",

abstract = "Background: Burkholderia pseudomallei is the causative agent of melioidosis, a potentially fatal disease endemic in Southeast Asia and Northern Australia. This Gram-negative pathogen possesses numerous virulence factors including three {"}injection type{"} type three secretion systems (T3SSs). B. pseudomallei has been shown to activate NFκB in HEK293T cells in a Toll-like receptor and MyD88 independent manner that requires T3SS gene cluster 3 (T3SS3 or T3SSBsa). However, the mechanism of how T3SS3 contributes to NFκB activation is unknown. Results: Known T3SS3 effectors are not responsible for NFκB activation. Furthermore, T3SS3-null mutants are able to activate NFκB almost to the same extent as wildtype bacteria at late time points of infection, corresponding to delayed escape into the cytosol. NFκB activation also occurs when bacteria are delivered directly into the cytosol by photothermal nanoblade injection. Conclusions: T3SS3 does not directly activate NFκB but facilitates bacterial escape into the cytosol where the host is able to sense the presence of the pathogen through cytosolic sensors leading to NFκB activation.",

author = "Teh, {Boon Eng} and French, {Christopher Todd} and Yahua Chen and Chen, {Isabelle Gek Joo} and Wu, {Ting Hsiang} and Enrico Sagullo and Chiou, {Pei Yu} and Teitell, {Michael A.} and Miller, {Jeff F.} and Gan, {Yunn Hwen}",

note = "Funding Information: We thank Mark P Stevens (Institute of Animal Health, UK) for the BopE and SopE expression plasmids and Peter Cheung (Nanyang Technological University) and Liu Xinyu (NUS) for technical advice on the TAK1 immunoprecipitations and Western blots. This work is funded by the Ministry of Education Tier 2 grant T208A3105, the National Medical Research Council grant NMRC/EDG/1052/2011 to YHG, the Defense Threat Reduction Agency (HDTRA1-11-1-0003) to JFM, the Pacific Southwest Regional Center of Excellence in Biodefense and Emerging Infectious Diseases (U54 A1065359) to JFM, the National Science Foundation CBET 0853500, ECCS 0901154, DBI-0852701 awards, University of California Discovery Biotechnology Award 178517, the National Institutes of Health Roadmap for Medical Research Nanomedicine Initiative PN2EY018228, NIH R21EB014456, and an Innovator Award from the Broad Stem Cell Research Center at UCLA.",

year = "2014",

month = may,

day = "6",

doi = "10.1186/1471-2180-14-115",

language = "English (US)",

volume = "14",

journal = "BMC microbiology",

issn = "1471-2180",

publisher = "BioMed Central",

number = "1",

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TY - JOUR

T1 - Type three secretion system-mediated escape of Burkholderia pseudomallei into the host cytosol is critical for the activation of NFκB

AU - Teh, Boon Eng

AU - French, Christopher Todd

AU - Chen, Yahua

AU - Chen, Isabelle Gek Joo

AU - Wu, Ting Hsiang

AU - Sagullo, Enrico

AU - Chiou, Pei Yu

AU - Teitell, Michael A.

AU - Miller, Jeff F.

AU - Gan, Yunn Hwen

N1 - Funding Information: We thank Mark P Stevens (Institute of Animal Health, UK) for the BopE and SopE expression plasmids and Peter Cheung (Nanyang Technological University) and Liu Xinyu (NUS) for technical advice on the TAK1 immunoprecipitations and Western blots. This work is funded by the Ministry of Education Tier 2 grant T208A3105, the National Medical Research Council grant NMRC/EDG/1052/2011 to YHG, the Defense Threat Reduction Agency (HDTRA1-11-1-0003) to JFM, the Pacific Southwest Regional Center of Excellence in Biodefense and Emerging Infectious Diseases (U54 A1065359) to JFM, the National Science Foundation CBET 0853500, ECCS 0901154, DBI-0852701 awards, University of California Discovery Biotechnology Award 178517, the National Institutes of Health Roadmap for Medical Research Nanomedicine Initiative PN2EY018228, NIH R21EB014456, and an Innovator Award from the Broad Stem Cell Research Center at UCLA.

PY - 2014/5/6

Y1 - 2014/5/6

N2 - Background: Burkholderia pseudomallei is the causative agent of melioidosis, a potentially fatal disease endemic in Southeast Asia and Northern Australia. This Gram-negative pathogen possesses numerous virulence factors including three "injection type" type three secretion systems (T3SSs). B. pseudomallei has been shown to activate NFκB in HEK293T cells in a Toll-like receptor and MyD88 independent manner that requires T3SS gene cluster 3 (T3SS3 or T3SSBsa). However, the mechanism of how T3SS3 contributes to NFκB activation is unknown. Results: Known T3SS3 effectors are not responsible for NFκB activation. Furthermore, T3SS3-null mutants are able to activate NFκB almost to the same extent as wildtype bacteria at late time points of infection, corresponding to delayed escape into the cytosol. NFκB activation also occurs when bacteria are delivered directly into the cytosol by photothermal nanoblade injection. Conclusions: T3SS3 does not directly activate NFκB but facilitates bacterial escape into the cytosol where the host is able to sense the presence of the pathogen through cytosolic sensors leading to NFκB activation.

AB - Background: Burkholderia pseudomallei is the causative agent of melioidosis, a potentially fatal disease endemic in Southeast Asia and Northern Australia. This Gram-negative pathogen possesses numerous virulence factors including three "injection type" type three secretion systems (T3SSs). B. pseudomallei has been shown to activate NFκB in HEK293T cells in a Toll-like receptor and MyD88 independent manner that requires T3SS gene cluster 3 (T3SS3 or T3SSBsa). However, the mechanism of how T3SS3 contributes to NFκB activation is unknown. Results: Known T3SS3 effectors are not responsible for NFκB activation. Furthermore, T3SS3-null mutants are able to activate NFκB almost to the same extent as wildtype bacteria at late time points of infection, corresponding to delayed escape into the cytosol. NFκB activation also occurs when bacteria are delivered directly into the cytosol by photothermal nanoblade injection. Conclusions: T3SS3 does not directly activate NFκB but facilitates bacterial escape into the cytosol where the host is able to sense the presence of the pathogen through cytosolic sensors leading to NFκB activation.

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U2 - 10.1186/1471-2180-14-115

DO - 10.1186/1471-2180-14-115

M3 - Article

AN - SCOPUS:84901435123

SN - 1471-2180

VL - 14

JO - BMC microbiology

JF - BMC microbiology

IS - 1

M1 - 115

ER -

Type three secretion system-mediated escape of Burkholderia pseudomallei into the host cytosol is critical for the activation of NFκB

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