The Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in <italic toggle="yes">Acinetobacter baumannii</italic>

ABSTRACT The type VI secretion system (T6SS) is a critical weapon in bacterial warfare between Gram-negative bacteria. Although invaluable for niche establishment, this machine represents an energetic burden to its host bacterium. Acinetobacter baumannii is an opportunistic pathogen that poses a ser...

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Autores principales:	Juvenal Lopez, Pek Man Ly, Mario F. Feldman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	T6SS T6SS assembly VgrG bacterial competition contractile injection system secretion systems Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a890efc317e74788985277e9807e9971
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spelling	oai:doaj.org-article:a890efc317e74788985277e9807e99712021-11-15T15:56:58ZThe Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in <italic toggle="yes">Acinetobacter baumannii</italic>10.1128/mBio.02761-192150-7511https://doaj.org/article/a890efc317e74788985277e9807e99712020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02761-19https://doaj.org/toc/2150-7511ABSTRACT The type VI secretion system (T6SS) is a critical weapon in bacterial warfare between Gram-negative bacteria. Although invaluable for niche establishment, this machine represents an energetic burden to its host bacterium. Acinetobacter baumannii is an opportunistic pathogen that poses a serious threat to public health due to its high rates of multidrug resistance. In some A. baumannii strains, the T6SS is transcriptionally downregulated by large multidrug resistance plasmids. Other strains, such as the clinical isolate AbCAN2, express T6SS-related genes but lack T6SS activity under laboratory conditions, despite not harboring these plasmids. This suggests that alternative mechanisms exist to repress the T6SS. Here, we used a transposon mutagenesis approach in AbCAN2 to identify novel T6SS repressors. Our screen revealed that the T6SS of this strain is inhibited by a homolog of VgrG, an essential structural component of all T6SSs reported to date. We named this protein inhibitory VgrG (VgrGi). Biochemical and in silico analyses demonstrated that the unprecedented inhibitory capability of VgrGi is due to a single amino acid mutation in a widely conserved C-terminal domain of unknown function, DUF2345. We also show that unlike in other bacteria, the C terminus of VgrG is essential for functional T6SS assembly in A. baumannii. Our study provides insight into the architectural requirements underlying functional assembly of the T6SS of A. baumannii. We propose that T6SS-inactivating point mutations are beneficial to the host bacterium, since they eliminate the energy cost associated with maintaining a functional T6SS, which appears to be unnecessary for A. baumannii virulence. IMPORTANCE Despite the clinical relevance of A. baumannii, little is known about its fundamental biology. Here, we show that a single amino acid mutation in VgrG, a critical T6SS structural protein, abrogates T6SS function. Given that this mutation was found in a clinical isolate, we propose that the T6SS of A. baumannii is probably not involved in virulence; this idea is supported by multiple genomic analyses showing that the majority of clinical A. baumannii strains lack proteins essential to the T6SS. We also show that, unlike in other species, the C terminus of VgrG is a unique architectural requirement for functional T6SS assembly in A. baumannii, suggesting that over evolutionary time, bacteria have developed changes to their T6SS architecture, leading to specialized systems.Juvenal LopezPek Man LyMario F. FeldmanAmerican Society for MicrobiologyarticleT6SST6SS assemblyVgrGbacterial competitioncontractile injection systemsecretion systemsMicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	T6SS T6SS assembly VgrG bacterial competition contractile injection system secretion systems Microbiology QR1-502
spellingShingle	T6SS T6SS assembly VgrG bacterial competition contractile injection system secretion systems Microbiology QR1-502 Juvenal Lopez Pek Man Ly Mario F. Feldman The Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in <italic toggle="yes">Acinetobacter baumannii</italic>
description	ABSTRACT The type VI secretion system (T6SS) is a critical weapon in bacterial warfare between Gram-negative bacteria. Although invaluable for niche establishment, this machine represents an energetic burden to its host bacterium. Acinetobacter baumannii is an opportunistic pathogen that poses a serious threat to public health due to its high rates of multidrug resistance. In some A. baumannii strains, the T6SS is transcriptionally downregulated by large multidrug resistance plasmids. Other strains, such as the clinical isolate AbCAN2, express T6SS-related genes but lack T6SS activity under laboratory conditions, despite not harboring these plasmids. This suggests that alternative mechanisms exist to repress the T6SS. Here, we used a transposon mutagenesis approach in AbCAN2 to identify novel T6SS repressors. Our screen revealed that the T6SS of this strain is inhibited by a homolog of VgrG, an essential structural component of all T6SSs reported to date. We named this protein inhibitory VgrG (VgrGi). Biochemical and in silico analyses demonstrated that the unprecedented inhibitory capability of VgrGi is due to a single amino acid mutation in a widely conserved C-terminal domain of unknown function, DUF2345. We also show that unlike in other bacteria, the C terminus of VgrG is essential for functional T6SS assembly in A. baumannii. Our study provides insight into the architectural requirements underlying functional assembly of the T6SS of A. baumannii. We propose that T6SS-inactivating point mutations are beneficial to the host bacterium, since they eliminate the energy cost associated with maintaining a functional T6SS, which appears to be unnecessary for A. baumannii virulence. IMPORTANCE Despite the clinical relevance of A. baumannii, little is known about its fundamental biology. Here, we show that a single amino acid mutation in VgrG, a critical T6SS structural protein, abrogates T6SS function. Given that this mutation was found in a clinical isolate, we propose that the T6SS of A. baumannii is probably not involved in virulence; this idea is supported by multiple genomic analyses showing that the majority of clinical A. baumannii strains lack proteins essential to the T6SS. We also show that, unlike in other species, the C terminus of VgrG is a unique architectural requirement for functional T6SS assembly in A. baumannii, suggesting that over evolutionary time, bacteria have developed changes to their T6SS architecture, leading to specialized systems.
format	article
author	Juvenal Lopez Pek Man Ly Mario F. Feldman
author_facet	Juvenal Lopez Pek Man Ly Mario F. Feldman
author_sort	Juvenal Lopez
title	The Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in <italic toggle="yes">Acinetobacter baumannii</italic>
title_short	The Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in <italic toggle="yes">Acinetobacter baumannii</italic>
title_full	The Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in <italic toggle="yes">Acinetobacter baumannii</italic>
title_fullStr	The Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in <italic toggle="yes">Acinetobacter baumannii</italic>
title_full_unstemmed	The Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in <italic toggle="yes">Acinetobacter baumannii</italic>
title_sort	tip of the vgrg spike is essential to functional type vi secretion system assembly in <italic toggle="yes">acinetobacter baumannii</italic>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/a890efc317e74788985277e9807e9971
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The Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in <italic toggle="yes">Acinetobacter baumannii</italic>

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