Charged Residues Flanking the Transmembrane Domain of Two Related Toxin-Antitoxin System Toxins Affect Host Response.

Andrew Holmes, Jessie Sadlon, Keith Weaver
Author Information
  1. Andrew Holmes: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
  2. Jessie Sadlon: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
  3. Keith Weaver: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.

Abstract

A majority of toxins produced by type I toxin-antitoxin (TA-1) systems are small membrane-localized proteins that were initially proposed to kill cells by forming non-specific pores in the cytoplasmic membrane. The examination of the effects of numerous TA-1 systems indicates that this is not the mechanism of action of many of these proteins. produces two toxins of the Fst/Ldr family, one encoded on pheromone-responsive conjugative plasmids (Fst) and the other on the chromosome, Fst. Previous results demonstrated that overexpression of the toxins produced a differential transcriptomic response in cells. In this report, we identify the specific amino acid differences between the two toxins responsible for the differential response of a gene highly induced by Fst but not Fst. In addition, we demonstrate that a transporter protein that is genetically linked to the chromosomal version of the TA-1 system functions to limit the toxicity of the protein.

Keywords

References

  1. J Biol Chem. 2012 Dec 21;287(52):43454-63 [PMID: 23129767]
  2. Mol Microbiol. 2000 Aug;37(3):652-60 [PMID: 10931358]
  3. Metabolites. 2012 Oct 16;2(4):756-74 [PMID: 24957761]
  4. Microbiology (Reading). 2010 Apr;156(Pt 4):975-977 [PMID: 20150240]
  5. J Bacteriol. 2006 Aug;188(15):5374-84 [PMID: 16855226]
  6. Mob Genet Elements. 2013 Sep 1;3(5):e26219 [PMID: 24251069]
  7. RNA Biol. 2012 Dec;9(12):1491-7 [PMID: 23059907]
  8. Microbiol Spectr. 2018 Jul;6(4): [PMID: 30051800]
  9. J Mol Model. 2017 Jul;23(7):206 [PMID: 28626846]
  10. PLoS Genet. 2009 Mar;5(3):e1000437 [PMID: 19325885]
  11. Curr Opin Microbiol. 2016 Apr;30:114-121 [PMID: 26874964]
  12. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8582-6 [PMID: 3936037]
  13. RNA Biol. 2012 Dec;9(12):1498-503 [PMID: 23059908]
  14. Proteins. 2011 Mar;79(3):898-915 [PMID: 21287621]
  15. Front Microbiol. 2018 Apr 25;9:814 [PMID: 29922242]
  16. J Bacteriol. 2010 Mar;192(6):1634-42 [PMID: 20097859]
  17. Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):20235-20243 [PMID: 32753384]
  18. Proc Natl Acad Sci U S A. 1986 May;83(10):3116-20 [PMID: 3517851]
  19. Mol Gen Genet. 1990 Oct;224(1):152-4 [PMID: 2126058]
  20. Microbiology (Reading). 2009 Sep;155(Pt 9):2930-2940 [PMID: 19542006]
  21. Biochemistry. 2010 Aug 10;49(31):6567-75 [PMID: 20677831]
  22. Annu Rev Biochem. 2014;83:753-77 [PMID: 24606146]
  23. Microbiol Mol Biol Rev. 2008 Dec;72(4):579-89, Table of Contents [PMID: 19052321]
  24. Antimicrob Agents Chemother. 2017 Apr 24;61(5): [PMID: 28223383]
  25. J Bacteriol. 2003 Apr;185(7):2169-77 [PMID: 12644486]
  26. Infect Immun. 2014 Sep;82(9):3599-611 [PMID: 24914223]
  27. Mol Microbiol. 1996 Apr;20(1):53-63 [PMID: 8861204]
  28. Toxins (Basel). 2020 Jul 25;12(8): [PMID: 32722354]
  29. Sci Rep. 2019 Oct 23;9(1):15208 [PMID: 31645607]
  30. J Mol Model. 2009 Oct;15(10):1213-9 [PMID: 19263093]
  31. J Bacteriol. 2009 Oct;191(20):6203-10 [PMID: 19684130]
  32. Nucleic Acids Res. 2010 Jun;38(11):3743-59 [PMID: 20156992]
  33. Mol Microbiol. 2015 Nov;98(4):651-66 [PMID: 26234942]
  34. Mol Microbiol. 2019 Jan;111(1):131-144 [PMID: 30276893]
  35. Toxins (Basel). 2019 May 09;11(5): [PMID: 31075979]
  36. Nucleic Acids Res. 2005 Feb 17;33(3):966-76 [PMID: 15718296]
  37. Comput Struct Biotechnol J. 2019 Jun 26;17:895-903 [PMID: 31333816]
  38. J Bacteriol. 2017 May 25;199(12): [PMID: 28348028]
  39. RNA Biol. 2012 Dec;9(12):1488-90 [PMID: 23324552]
  40. FEBS Lett. 2012 Jul 30;586(16):2529-34 [PMID: 22728134]
  41. Adv Biosyst. 2020 Mar;4(3):e1900290 [PMID: 32293143]
  42. Mob Genet Elements. 2011 Nov 1;1(4):283-290 [PMID: 22545240]
  43. Mol Cell. 2018 Jun 7;70(5):768-784 [PMID: 29398446]
  44. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3479-83 [PMID: 98769]
  45. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4784-8 [PMID: 6308648]
  46. J Bacteriol. 2013 Jan;195(1):156-66 [PMID: 23104812]

Grants

  1. R21 AI140037/NIAID NIH HHS
  2. AI140037/NIH HHS

MeSH Term

Amino Acid Sequence
Bacterial Toxins
Enterococcus faecalis
Gene Expression Regulation, Bacterial
Protein Domains
Toxin-Antitoxin Systems

Chemicals

Bacterial Toxins

Word Cloud

Created with Highcharts 10.0.0toxinsFstTA-1proteinproducedtypesystemssmallproteinscellstwoFst/Ldrfamilydifferentialresponsesystemmajoritytoxin-antitoxinmembrane-localizedinitiallyproposedkillformingnon-specificporescytoplasmicmembraneexaminationeffectsnumerousindicatesmechanismactionmanyproducesoneencodedpheromone-responsiveconjugativeplasmidschromosomePreviousresultsdemonstratedoverexpressiontranscriptomicreportidentifyspecificaminoaciddifferencesresponsiblegenehighlyinducedadditiondemonstratetransportergeneticallylinkedchromosomalversionfunctionslimittoxicityChargedResiduesFlankingTransmembraneDomainTwoRelatedToxin-AntitoxinSystemToxinsAffectHostResponseEnterococcusfaecalistoxin43toxin–antitoxin2

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