CoChat
Sign Up
PreprintCited by 20Bacterial Genetics and BiotechnologyEscherichia coli research studiesBacteriophages and microbial interactions

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Characterization of TelE, a T7SS LXG effector exhibiting a conserved C-terminal glycine zipper motif required for toxicity

Open access
Teh, Wooi Keong, Ding, Yichen, Gubellini, Francesca, Filloux, Alain, Poyart, Claire, Givskov, Michael, Dramsi, Shaynoor·2022·Microbiology Spectrum
DOI 10.1101/2022.09.07.506920PMC PMC10434224

Preprint — published as 10.1128/spectrum.01481-23

Open this paper in CoChat — free account

Abstract

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. Comparison of the proteins secreted by UCN34 WT 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 displaying pore-forming activity. 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 pore-forming activity. Unlike other pore-forming toxins commonly antagonized by a membrane protein, 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 pore-forming activity against non-immune bacteria. IMPORTANCE: In this study, 38 clinical isolates of Streptococcus gallolyticus subsp . gallolyticus ( SGG ) were sequenced and a genetic locus encoding the Type VIIb secretion system (T7SSb) was found conserved and absent from 16 genomes of the closely related S. gallolyticus subsp. pasteurianus (SGP) . The T7SSb is a bona fide pathogenicity island. Here, we report that the model organism SGG strain UCN34 secretes six T7SSb effectors. One of the six effectors named TelE displayed a strong toxicity when overexpressed in Escherichia coli . Our results indicate that TelE is a pore forming toxin whose activity can be antagonized by a non-canonical immunity protein named TipE. Overall, we report a unique toxin-immunity protein pair and our data expand the range of effectors secreted through T7SSb.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2022.09.07.506920

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 74

  1. 10.1128/JB.01659-09 · DOI
  2. 2014, Is colonoscopy necessary in cases of infection by Streptococcus bovis biotype II?, Eur J Clin Microbiol Infect Dis, 33, 171, 10.1007/s10096-013-1940-7 · DOI
  3. 10.1093/cid/cis434 · DOI
  4. 10.1016/j.jinf.2015.05.005 · DOI
  5. 10.3343/kjlm.2010.30.2.160 · DOI
  6. 2018, Association between bacteremia from specific microbes and subsequent diagnosis of colorectal cancer, Gastroenterology, 155, 383, 10.1053/j.gastro.2018.04.028 · DOI · Paper page
  7. 2006, Unusual bacterial infections and colorectal carcinoma - Streptococcus bovis and Clostridium septicum: Report of three cases, Diseases of the Colon & Rectum, 49, 1223, 10.1007/s10350-006-0576-4 · DOI
  8. 10.1093/cid/cir609 · DOI · Paper page
  9. 10.1097/MD.0000000000001708 · DOI
  10. 10.1128/JCM.02977-15 · DOI
  11. 2003, Reappraisal of the taxonomy of the Streptococcus bovis/Streptococcus equinus complex and related species: Description of Streptococcus gallolyticus subsp. gallolyticus subsp. nov, S. gallolyticus subsp. macedonicus subsp. nov. and S. gallolyticus subsp. pasteurianus subsp. nov. Int J Syst Evol Microbiol, 53, 631
  12. 10.1099/jmm.0.006551-0 · DOI
  13. 10.1016/j.jmii.2020.07.004 · DOI
  14. 10.1128/AEM.68.12.5891-5903.2002 · DOI
  15. 10.1016/j.ijfoodmicro.2009.05.012 · DOI
  16. 2016, The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria, Nat Microbiol, 2, 16183, 10.1038/nmicrobiol.2016.183 · DOI
  17. Anderson M , Ohr RJ , Aly KA , Nocadello S , Kim HK , Schneewind CE , Schneewind O , Missiakas D . 2017. EssE promotes Staphylococcus aureus ESS-dependent Protein secretion to modify host immune responses during infection. J Bacteriol 199. · DOI
  18. Whitney JC , Peterson SB , Kim J , Pazos M , Verster AJ , Radey MC , Kulasekara HD , Ching MQ , Bullen NP , Bryant D , Goo YA , Surette MG , Borenstein E , Vollmer W , Mougous JD . 2017. A broadly distributed toxin family mediates contact-dependent antagonism between Gram-positive bacteria. Elife 6. · DOI
  19. 10.1128/JB.01096-10 · DOI
  20. 10.1016/j.tim.2016.11.004 · DOI
  21. 10.1038/nrmicro1773 · DOI · Paper page
  22. 10.1073/pnas.0405620102 · DOI
  23. 10.1111/mmi.12395 · DOI
  24. 10.1111/j.1365-2958.2008.06324.x · DOI
  25. 10.1073/pnas.2006110117 · DOI
  26. 2017, A Novel ESAT-6 Secretion System-Secreted Protein EsxX of community-associated Staphylococcus aureus lineage ST398 contributes to immune evasion and virulence, Front Microbiol, 8, 819, 10.3389/fmicb.2017.00819 · DOI
  27. 10.1016/j.febslet.2011.12.020 · DOI
  28. 2022, Dual targeting factors are required for LXG toxin export by the bacterial Type VIIb Secretion System, mBio, 13, e0213722, 10.1128/mbio.02137-22 · DOI
  29. Ohr RJ , Anderson M , Shi M , Schneewind O , Missiakas D . 2017. EssD, a nuclease effector of the Staphylococcus aureus ESS pathway. J Bacteriol 199. · DOI
  30. 10.1371/journal.ppat.1009182 · DOI
  31. 10.1128/mBio.00285-15 · DOI
  32. 10.1073/pnas.0501234102 · DOI
  33. 2018, Conditional toxicity and synergy drive diversity among antibacterial effectors, Nat Microbiol, 3, 440, 10.1038/s41564-018-0113-y · DOI
  34. 2020, A comparative genomics methodology reveals a widespread family of membrane-disrupting T6SS effectors, Nat Commun, 11, 1085, 10.1038/s41467-020-14951-4 · DOI
  35. 10.1073/pnas.1601375113 · DOI
  36. 10.1101/2020.12.06.413849:2020.12.06.413849 · DOI
  37. 2018, Molecular basis for immunity protein recognition of a Type VII Secretion System exported antibacterial toxin, J Mol Biol, 430, 4344, 10.1016/j.jmb.2018.08.027 · DOI
  38. Garcia-Bayona L , Guo MS , Laub MT . 2017. Contact-dependent killing by Caulobacter crescentus via cell surface-associated, glycine zipper proteins. Elife 6. · DOI
  39. 10.1074/jbc.M212595200 · DOI
  40. 10.1073/pnas.1715112115 · DOI
  41. 10.1158/0008-5472.CAN-07-0824 · DOI
  42. 10.1016/j.canlet.2008.11.016 · DOI
  43. 10.1126/science.1224820 · DOI · Paper page
  44. 10.1073/pnas.1001261107 · DOI · Paper page
  45. 2020, Mutational signature in colorectal cancer caused by genotoxic pks(+) E. coli, Nature, 580, 269, 10.1038/s41586-020-2080-8 · DOI · Paper page
  46. 10.1084/jem.179.5.1653 · DOI
  47. Teh WK , Dramsi S , Tolker-Nielsen T , Yang L , Givskov M . 2019. Increased intracellular cyclic di-AMP levels sensitize Streptococcus gallolyticus subsp. gallolyticus to osmotic stress and reduce biofilm formation and adherence on intestinal cells. J Bacteriol 201. · DOI
  48. Green MR , Sambrook J , Sambrook J . 2012. Molecular cloning: A laboratory manual, 4th ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
  49. 10.1016/0378-1119(90)90336-P · DOI
  50. 10.1016/j.resmic.2013.09.002 · DOI
  51. 10.1006/jmbi.2001.5294 · DOI
  52. 10.1128/AEM.57.4.1194-1201.1991 · DOI
  53. 10.1128/jb.175.11.3628-3635.1993 · DOI
  54. 10.1128/JB.00230-13 · DOI
  55. 10.1186/1471-2164-9-75 · DOI
  56. 10.1038/srep08365 · DOI
  57. 10.1093/nar/gkt1226 · DOI
  58. 10.1186/s13059-014-0524-x · DOI
  59. 10.1371/journal.pone.0009490 · DOI · Paper page
  60. 10.1186/1471-2164-12-402 · DOI
  61. 2017, IslandViewer 4: Expanded prediction of genomic islands for larger-scale datasets, 45, W30
  62. 10.1093/bioinformatics/btr039 · DOI
  63. 2017, Identification of effectors: Precipitation of supernatant material, Methods Mol Biol, 1615, 459, 10.1007/978-1-4939-7033-9_31 · DOI
  64. 10.1016/1044-0305(94)80016-2 · DOI · Paper page
  65. 10.1038/nprot.2017.147 · DOI
  66. 10.1093/bioinformatics/18.suppl_1.S96 · DOI · Paper page
  67. 10.1021/acs.jproteome.5b00981 · DOI
  68. 10.1038/nprot.2010.5 · DOI
  69. 10.1038/nmeth.3213 · DOI · Paper page
  70. 10.1093/nar/gkv342 · DOI
  71. 10.1093/bib/bbx108 · DOI · Paper page
  72. 10.1093/nar/gkt389 · DOI
  73. 10.1093/nar/gks469 · DOI
  74. 10.1093/bioinformatics/14.4.380 · DOI

Metadata

Authors
Teh, W. K., Ding, Y., Gubellini, F., Filloux, A., Poyart, C., Givskov, M., & Dramsi, S.
Affiliations
  • Nanyang Technological University (SG)
  • Temasek Life Sciences Laboratory (SG)
  • Institut Pasteur (FR)
  • Université Paris Cité (FR)
  • University of Copenhagen (DK)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
  • Givskov, Michael
  • Dramsi, Shaynoor
ORCID
Venue
Microbiology Spectrum
Publisher
openRxiv
Published
2022-09-07
Volume
11
Issue
4
Pages
e0148123-e0148123
ISSN
2165-0497 (ISSN-L)
DOI
10.1101/2022.09.07.506920
PMC
PMC10434224
OpenAlex
W4383872731
Cited by
20
References
1
Citations by year
2026: 4 · 2025: 6 · 2024: 6 · 2023: 4
FWCI
3.32
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Microbiology Spectrum (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DR-NTU (Nanyang Technological University) (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Funders
  • National Research Foundation
  • Agence Nationale de la Recherche (10-LABX-62-IBEID, ANR‐10‐LABX‐62‐IBEID, ANR-LABX-62-IBEID, ANR-10, ANR-10-LABX-0062, ANR-10-LABX-62)
  • Institut National Du Cancer (PLBIO16-025)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
Keywords
tele, TIPE, type III secretion system, effector proteins, pore-forming toxins, bacterial virulence
MeSH terms
Type VII Secretion Systems, Streptococcus gallolyticus subspecies gallolyticus, Glycine, Amino Acid Motifs

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review