Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif)
Cycle inhibiting factors (Cifs) are type III secretion system effectors produced by some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Through their deamidase activity, Cifs inhibit the activity of Cullin RING E3 ubiquitin ligases (CRL). CRL inhibition induces the accumulati...
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doaj-f97f89e2db9f463ba17653732f1205c52021-06-02T14:18:20ZengThe Company of BiologistsBiology Open2046-63902018-07-017710.1242/bio.028225028225Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif)Mei Ying Ng0Yunn-Hwen Gan1Thilo Hagen2 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore Cycle inhibiting factors (Cifs) are type III secretion system effectors produced by some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Through their deamidase activity, Cifs inhibit the activity of Cullin RING E3 ubiquitin ligases (CRL). CRL inhibition induces the accumulation of cell cycle inhibitors p21 and p27, thereby leading to host cell cycle arrest. However, whether Cif exerts additional effects on host cells that are important in bacterial pathogenesis is currently poorly understood. In this study, we found that Cif exerts a bimodal effect on NF-κB signalling. Cif increases basal NF-κB activity. This effect is dependent on Cif-mediated activation of ERK MAPK. On the other hand, Cif inhibits NF-κB activation by TNFα and Burkholderia thailandensis infection. This inhibitory effect on NF-κB activity is partially mediated by Cif-dependent inhibition of CRLs. We also found that Cif only has a modest effect in stimulating the intracellular replication of the B. pseudomallei surrogate, B. thailandensis. The observed Cif-dependent stimulation of B. thailandensis intracellular replication was not, or was only partially, due to CRL inhibition. Furthermore, the increased B. thailandensis replication induced by Cif was independent of ERK MAPK activation. Our findings suggest that Cif likely exerts additional cellular effects through novel targets.http://bio.biologists.org/content/7/7/bio028225Burkholderia pseudomalleiCycle inhibiting factorCullin RING E3 ubiquitin ligaseNF-κB |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mei Ying Ng Yunn-Hwen Gan Thilo Hagen |
spellingShingle |
Mei Ying Ng Yunn-Hwen Gan Thilo Hagen Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif) Biology Open Burkholderia pseudomallei Cycle inhibiting factor Cullin RING E3 ubiquitin ligase NF-κB |
author_facet |
Mei Ying Ng Yunn-Hwen Gan Thilo Hagen |
author_sort |
Mei Ying Ng |
title |
Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif) |
title_short |
Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif) |
title_full |
Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif) |
title_fullStr |
Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif) |
title_full_unstemmed |
Characterisation of cellular effects of Burkholderia pseudomallei cycle inhibiting factor (Cif) |
title_sort |
characterisation of cellular effects of burkholderia pseudomallei cycle inhibiting factor (cif) |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2018-07-01 |
description |
Cycle inhibiting factors (Cifs) are type III secretion system effectors produced by some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Through their deamidase activity, Cifs inhibit the activity of Cullin RING E3 ubiquitin ligases (CRL). CRL inhibition induces the accumulation of cell cycle inhibitors p21 and p27, thereby leading to host cell cycle arrest. However, whether Cif exerts additional effects on host cells that are important in bacterial pathogenesis is currently poorly understood. In this study, we found that Cif exerts a bimodal effect on NF-κB signalling. Cif increases basal NF-κB activity. This effect is dependent on Cif-mediated activation of ERK MAPK. On the other hand, Cif inhibits NF-κB activation by TNFα and Burkholderia thailandensis infection. This inhibitory effect on NF-κB activity is partially mediated by Cif-dependent inhibition of CRLs. We also found that Cif only has a modest effect in stimulating the intracellular replication of the B. pseudomallei surrogate, B. thailandensis. The observed Cif-dependent stimulation of B. thailandensis intracellular replication was not, or was only partially, due to CRL inhibition. Furthermore, the increased B. thailandensis replication induced by Cif was independent of ERK MAPK activation. Our findings suggest that Cif likely exerts additional cellular effects through novel targets. |
topic |
Burkholderia pseudomallei Cycle inhibiting factor Cullin RING E3 ubiquitin ligase NF-κB |
url |
http://bio.biologists.org/content/7/7/bio028225 |
work_keys_str_mv |
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