Identification of novel Acinetobacter baumannii type VI secretion system antibacterial effector and immunity pairs

Timothy C. Fitzsimons, Jessica M. Lewis, Amy Wright, Oded Kleifeld, Ralf B. Schittenhelm, David Powell, Marina Harper, John D. Boyce

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The type VI secretion system (T6SS) is a macromolecular machine that delivers protein effectors into host cells and/or competing bacteria. The effectors may be delivered as noncovalently bound cargo of T6SS needle proteins (VgrG/Hcp/ PAAR) or as C-terminal extensions of these proteins. Many Acinetobacter baumannii strains produce a T6SS, but little is known about the specific effectors or how they are delivered. In this study, we show that A. baumannii AB307-0294 encodes three vgrG loci, each containing a vgrG gene, a T6SS toxic effector gene, and an antitoxin/ immunity gene. Each of the T6SS toxic effectors could kill Escherichia coli when produced in trans unless the cognate immunity protein was coproduced. To determine the role of each VgrG in effector delivery, we performed interbacterial competitive killing assays using A. baumannii AB307-0294 vgrG mutants, together with Acinetobacter baylyi prey cells expressing pairs of immunity genes that protected against two toxic effectors but not a third. Using this approach, we showed that AB307- 0294 produces only three T6SS toxic effectors capable of killing A. baylyi and that each VgrG protein is specific for the carriage of one effector. Finally, we analyzed a number of A. baumannii genomes and identified significant diversity in the range of encoded T6SS VgrG and effector proteins, with correlations between effector types and A. baumannii global clone lineages.

Original languageEnglish
Article numbere00297-18
Number of pages23
JournalInfection and Immunity
Volume86
Issue number8
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • Acinetobacter baumannii
  • Antibacterial toxins
  • Effector functions
  • Effectors
  • Type VI secretion system

Cite this

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title = "Identification of novel Acinetobacter baumannii type VI secretion system antibacterial effector and immunity pairs",
abstract = "The type VI secretion system (T6SS) is a macromolecular machine that delivers protein effectors into host cells and/or competing bacteria. The effectors may be delivered as noncovalently bound cargo of T6SS needle proteins (VgrG/Hcp/ PAAR) or as C-terminal extensions of these proteins. Many Acinetobacter baumannii strains produce a T6SS, but little is known about the specific effectors or how they are delivered. In this study, we show that A. baumannii AB307-0294 encodes three vgrG loci, each containing a vgrG gene, a T6SS toxic effector gene, and an antitoxin/ immunity gene. Each of the T6SS toxic effectors could kill Escherichia coli when produced in trans unless the cognate immunity protein was coproduced. To determine the role of each VgrG in effector delivery, we performed interbacterial competitive killing assays using A. baumannii AB307-0294 vgrG mutants, together with Acinetobacter baylyi prey cells expressing pairs of immunity genes that protected against two toxic effectors but not a third. Using this approach, we showed that AB307- 0294 produces only three T6SS toxic effectors capable of killing A. baylyi and that each VgrG protein is specific for the carriage of one effector. Finally, we analyzed a number of A. baumannii genomes and identified significant diversity in the range of encoded T6SS VgrG and effector proteins, with correlations between effector types and A. baumannii global clone lineages.",
keywords = "Acinetobacter baumannii, Antibacterial toxins, Effector functions, Effectors, Type VI secretion system",
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Identification of novel Acinetobacter baumannii type VI secretion system antibacterial effector and immunity pairs. / Fitzsimons, Timothy C.; Lewis, Jessica M.; Wright, Amy; Kleifeld, Oded; Schittenhelm, Ralf B.; Powell, David; Harper, Marina; Boyce, John D.

In: Infection and Immunity, Vol. 86, No. 8, e00297-18, 01.08.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Identification of novel Acinetobacter baumannii type VI secretion system antibacterial effector and immunity pairs

AU - Fitzsimons, Timothy C.

AU - Lewis, Jessica M.

AU - Wright, Amy

AU - Kleifeld, Oded

AU - Schittenhelm, Ralf B.

AU - Powell, David

AU - Harper, Marina

AU - Boyce, John D.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - The type VI secretion system (T6SS) is a macromolecular machine that delivers protein effectors into host cells and/or competing bacteria. The effectors may be delivered as noncovalently bound cargo of T6SS needle proteins (VgrG/Hcp/ PAAR) or as C-terminal extensions of these proteins. Many Acinetobacter baumannii strains produce a T6SS, but little is known about the specific effectors or how they are delivered. In this study, we show that A. baumannii AB307-0294 encodes three vgrG loci, each containing a vgrG gene, a T6SS toxic effector gene, and an antitoxin/ immunity gene. Each of the T6SS toxic effectors could kill Escherichia coli when produced in trans unless the cognate immunity protein was coproduced. To determine the role of each VgrG in effector delivery, we performed interbacterial competitive killing assays using A. baumannii AB307-0294 vgrG mutants, together with Acinetobacter baylyi prey cells expressing pairs of immunity genes that protected against two toxic effectors but not a third. Using this approach, we showed that AB307- 0294 produces only three T6SS toxic effectors capable of killing A. baylyi and that each VgrG protein is specific for the carriage of one effector. Finally, we analyzed a number of A. baumannii genomes and identified significant diversity in the range of encoded T6SS VgrG and effector proteins, with correlations between effector types and A. baumannii global clone lineages.

AB - The type VI secretion system (T6SS) is a macromolecular machine that delivers protein effectors into host cells and/or competing bacteria. The effectors may be delivered as noncovalently bound cargo of T6SS needle proteins (VgrG/Hcp/ PAAR) or as C-terminal extensions of these proteins. Many Acinetobacter baumannii strains produce a T6SS, but little is known about the specific effectors or how they are delivered. In this study, we show that A. baumannii AB307-0294 encodes three vgrG loci, each containing a vgrG gene, a T6SS toxic effector gene, and an antitoxin/ immunity gene. Each of the T6SS toxic effectors could kill Escherichia coli when produced in trans unless the cognate immunity protein was coproduced. To determine the role of each VgrG in effector delivery, we performed interbacterial competitive killing assays using A. baumannii AB307-0294 vgrG mutants, together with Acinetobacter baylyi prey cells expressing pairs of immunity genes that protected against two toxic effectors but not a third. Using this approach, we showed that AB307- 0294 produces only three T6SS toxic effectors capable of killing A. baylyi and that each VgrG protein is specific for the carriage of one effector. Finally, we analyzed a number of A. baumannii genomes and identified significant diversity in the range of encoded T6SS VgrG and effector proteins, with correlations between effector types and A. baumannii global clone lineages.

KW - Acinetobacter baumannii

KW - Antibacterial toxins

KW - Effector functions

KW - Effectors

KW - Type VI secretion system

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U2 - 10.1128/IAI.00297-18

DO - 10.1128/IAI.00297-18

M3 - Article

VL - 86

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

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