Characterization of TelE, a T7SS LXG effector exhibiting a conserved C-terminal glycine zipper motif required for toxicity
Streptococcus gallolyticus subsp. gallolyticus (SGG) is an opportunistic bacterial pathogen strongly associated with colorectal cancer. Here, through comparative genomics analysis, we demonstrated that the genetic locus encoding the type VIIb secretion system (T7SSb) machinery is uniquely present in...
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sg-ntu-dr.10356-1716652023-11-09T15:30:28Z Characterization of TelE, a T7SS LXG effector exhibiting a conserved C-terminal glycine zipper motif required for toxicity Teh, Wooi Keong Ding, Yichen Gubellini, Francesca Filloux, Alain Poyart, Claire Givskov, Michael Dramsi, Shaynoor Singapore Centre for Environmental Life Sciences and Engineering Engineering::Environmental engineering Streptococcus Gallolyticus Pore-forming Toxin Streptococcus gallolyticus subsp. gallolyticus (SGG) is an opportunistic bacterial pathogen strongly associated with colorectal cancer. Here, through comparative genomics analysis, we demonstrated that the genetic locus encoding the type VIIb secretion system (T7SSb) machinery is uniquely present in SGG in two different arrangements. SGG UCN34 carrying the most prevalent T7SSb genetic arrangement was chosen as the reference strain. To identify the effectors secreted by this secretion system, we inactivated the essC gene encoding the motor of this machinery. A comparison of the proteins secreted by UCN34 wild type and its isogenic ΔessC mutant revealed six T7SSb effector proteins, including the expected WXG effector EsxA and three LXG-containing proteins. In this work, we characterized an LXG-family toxin named herein TelE promoting the loss of membrane integrity. Seven homologs of TelE harboring a conserved glycine zipper motif at the C terminus were identified in different SGG isolates. Scanning mutagenesis of this motif showed that the glycine residue at position 470 was crucial for TelE membrane destabilization activity. TelE activity was antagonized by a small protein TipE belonging to the DUF5085 family. Overall, we report herein a unique SGG T7SSb effector exhibiting a toxic activity against nonimmune bacteria. Ministry of Education (MOE) National Research Foundation (NRF) Published version This work was supported by the National Research Foundation and Ministry of Education Singapore under its Research Centre of Excellence Program (SCELSE). S. Dramsi acknowledges the support of the Institut National contre le Cancer (INCA; grant PLBIO16-025) and from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant no. ANR-10-LABX-62-IBEID). A. Filloux acknowledges the support of Singapore Centre for Environmental Life Sciences Engineering (SCELSE; grant no. 04MNS001779A660OOE01). 2023-11-03T06:47:10Z 2023-11-03T06:47:10Z 2023 Journal Article Teh, W. K., Ding, Y., Gubellini, F., Filloux, A., Poyart, C., Givskov, M. & Dramsi, S. (2023). Characterization of TelE, a T7SS LXG effector exhibiting a conserved C-terminal glycine zipper motif required for toxicity. Microbiology Spectrum, 11(4), e0148123-. https://dx.doi.org/10.1128/spectrum.01481-23 2165-0497 https://hdl.handle.net/10356/171665 10.1128/spectrum.01481-23 37432124 2-s2.0-85168247750 4 11 e0148123 en 04MNS001779A660OOE01 Microbiology Spectrum © 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0International license. application/pdf |
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Engineering::Environmental engineering Streptococcus Gallolyticus Pore-forming Toxin Teh, Wooi Keong Ding, Yichen Gubellini, Francesca Filloux, Alain Poyart, Claire Givskov, Michael Dramsi, Shaynoor Characterization of TelE, a T7SS LXG effector exhibiting a conserved C-terminal glycine zipper motif required for toxicity |
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Streptococcus gallolyticus subsp. gallolyticus (SGG) is an opportunistic bacterial pathogen strongly associated with colorectal cancer. Here, through comparative genomics analysis, we demonstrated that the genetic locus encoding the type VIIb secretion system (T7SSb) machinery is uniquely present in SGG in two different arrangements. SGG UCN34 carrying the most prevalent T7SSb genetic arrangement was chosen as the reference strain. To identify the effectors secreted by this secretion system, we inactivated the essC gene encoding the motor of this machinery. A comparison of the proteins secreted by UCN34 wild type and its isogenic ΔessC mutant revealed six T7SSb effector proteins, including the expected WXG effector EsxA and three LXG-containing proteins. In this work, we characterized an LXG-family toxin named herein TelE promoting the loss of membrane integrity. Seven homologs of TelE harboring a conserved glycine zipper motif at the C terminus were identified in different SGG isolates. Scanning mutagenesis of this motif showed that the glycine residue at position 470 was crucial for TelE membrane destabilization activity. TelE activity was antagonized by a small protein TipE belonging to the DUF5085 family. Overall, we report herein a unique SGG T7SSb effector exhibiting a toxic activity against nonimmune bacteria. |
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Singapore Centre for Environmental Life Sciences and Engineering |
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Singapore Centre for Environmental Life Sciences and Engineering Teh, Wooi Keong Ding, Yichen Gubellini, Francesca Filloux, Alain Poyart, Claire Givskov, Michael Dramsi, Shaynoor |
format |
Article |
author |
Teh, Wooi Keong Ding, Yichen Gubellini, Francesca Filloux, Alain Poyart, Claire Givskov, Michael Dramsi, Shaynoor |
author_sort |
Teh, Wooi Keong |
title |
Characterization of TelE, a T7SS LXG effector exhibiting a conserved C-terminal glycine zipper motif required for toxicity |
title_short |
Characterization of TelE, a T7SS LXG effector exhibiting a conserved C-terminal glycine zipper motif required for toxicity |
title_full |
Characterization of TelE, a T7SS LXG effector exhibiting a conserved C-terminal glycine zipper motif required for toxicity |
title_fullStr |
Characterization of TelE, a T7SS LXG effector exhibiting a conserved C-terminal glycine zipper motif required for toxicity |
title_full_unstemmed |
Characterization of TelE, a T7SS LXG effector exhibiting a conserved C-terminal glycine zipper motif required for toxicity |
title_sort |
characterization of tele, a t7ss lxg effector exhibiting a conserved c-terminal glycine zipper motif required for toxicity |
publishDate |
2023 |
url |
https://hdl.handle.net/10356/171665 |
_version_ |
1783955608646451200 |