A DNase Type VI Secretion System Effector Requires Its MIX Domain for Secretion

Fridman, Chaya Mushka; Jana, Biswanath; Ben-Yaakov, Rotem; Bosis, Eran; Salomon, Dor

doi:10.1128/spectrum.02465-22

Cited by 10 publications

(14 citation statements)

References 60 publications

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“…Collectively, we discovered A. tumefaciens strain 1D1609 is equipped with two T6SS nuclease effectors, V2a and V2c, that belong to His-Me finger superfamily. The findings expand the variety of T6SS His-Me finger nucleases on top of those have been functionally characterized (9, 17, 18, 19).…”

Section: Discussionsupporting

confidence: 52%

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Agrobacteria deploy two classes of His-Me finger superfamily nuclease effectors exerting different antibacterial capacities against specific bacterial competitors

Santos¹,

Pintor²,

Hsieh

et al. 2023

Preprint

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Type VI secretion system (T6SS) assembles into a contractile nanomachine to inject effectors across bacterial membranes for secretion. Agrobacterium tumefaciens species complex is a group of soil inhabitants and phytopathogens that deploys T6SS as an antibacterial weapon against bacterial competitors at both inter-species and intra-species levels. A. tumefaciens strain 1D1609 genome encodes four effector genes, in which all four are specialized effector harboring a conserved N-terminal PAAR-like DUF4150 domain but distinct C-terminal effector domains. Previous study reported that V2a is a His-Me finger nuclease toxin contributing to DNase-mediated antibacterial activity. However, it remains unknown about the functions and roles of other three effectors. In this study, we identified V2c is another His-Me finger nuclease encoded by 1D1609 genome but with distinct SHH motif differed from AHH motif of V2a. We demonstrated that the ectopic expression of V2c caused growth inhibition, plasmid DNA degradation, and cell elongation in Escherichia coli. The cognate immunity protein, V3c, neutralizes the DNase activity and rescues phenotypes of the growth inhibition and cell elongation. Ectopic expression of V2c DNase-inactive variants retain the cell elongation phenotype while V2a induced cell elongation in a DNase-mediated manner. We also showed that the amino acids of conserved SHH and HNH motifs are responsible for the V2c DNase activity in vivo and in vitro. Notably, V2c also mediated the DNA degradation and cell elongation of target cell in the context of interbacterial competition. Importantly, V2a and V2c function synergistically to exert stronger antibacterial activity against the soft rot phytopathogen, Dickeya dadantii.

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Section: Discussionsupporting

confidence: 52%

“…The findings expand the variety of T6SS His-Me finger nucleases on top of those have been functionally characterized (9,17,18,19).…”

Section: Santos Et Al His-me Finger T6ss Nuclease Toxinsmentioning

confidence: 56%

Agrobacteria deploy two classes of His-Me finger superfamily nuclease effectors exerting different antibacterial capacities against specific bacterial competitors

Santos¹,

Pintor²,

Hsieh

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…MIX appears to be mainly located at the N-terminal region of the proteins, fused to C-terminal effector domains with antibacterial or anti-eukaryotic activity ( Salomon et al., 2014 ). A recent work has shown that MIX sequence is necessary for the translocation of the effector from T6SS1 of Vibrio parahaemolyticus , demonstrating the importance of this signal in substrate recruitment ( Fridman et al., 2022 ). Recently, it has been proposed that these sequences can be found not only in the effector protein, but also in a co-effector, which enables the loading and secretion of the toxin via the T6SS ( Dar et al., 2022 ).…”

Section: Structure Substrate Recruitment and Secretion Mechanismmentioning

confidence: 99%

Recruitment of heterologous substrates by bacterial secretion systems for transkingdom translocation

Guzmán-Herrador

Fernández-Gómez²,

Llosa³

2023

Front. Cell. Infect. Microbiol.

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Bacterial secretion systems mediate the selective exchange of macromolecules between bacteria and their environment, playing a pivotal role in processes such as horizontal gene transfer or virulence. Among the different families of secretion systems, Type III, IV and VI (T3SS, T4SS and T6SS) share the ability to inject their substrates into human cells, opening up the possibility of using them as customized injectors. For this to happen, it is necessary to understand how substrates are recruited and to be able to engineer secretion signals, so that the transmembrane machineries can recognize and translocate the desired substrates in place of their own. Other factors, such as recruiting proteins, chaperones, and the degree of unfolding required to cross through the secretion channel, may also affect transport. Advances in the knowledge of the secretion mechanism have allowed heterologous substrate engineering to accomplish translocation by T3SS, and to a lesser extent, T4SS and T6SS into human cells. In the case of T4SS, transport of nucleoprotein complexes adds a bonus to its biotechnological potential. Here, we review the current knowledge on substrate recognition by these secretion systems, the many examples of heterologous substrate translocation by engineering of secretion signals, and the current and future biotechnological and biomedical applications derived from this approach.

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“…dadantii , inducing loss of DAPI (4′,6-diamidino-2-phenylindole) staining in target cells and leading to plasmid degradation in overexpressing bacteria ( Koskiniemi et al ., 2013 ). Other organisms that encode T6SS effectors from the His-Me superfamily are Vibrio parahaemolyticus ( Salomon et al ., 2014 ; Fridman et al ., 2022 ), Serratia marcescens ( Alcoforado-Diniz and Coulthurst, 2015 ), Acinetobacter baumannii ( Fitzsimons et al ., 2018 ), E . coli ( Nipič et al ., 2013 ; Ma et al ., 2017 ), Aeromonas dhakensis ( Pei et al ., 2020 ), and Pseudomonas spp .…”

Section: His-me Finger Superfamilymentioning

confidence: 99%

Intercepting biological messages: Antibacterial molecules targeting nucleic acids during interbacterial conflicts

et al. 2023

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Bacteria live in polymicrobial communities and constantly compete for resources. These organisms have evolved an array of antibacterial weapons to inhibit the growth or kill competitors. The arsenal comprises antibiotics, bacteriocins, and contact-dependent effectors that are either secreted in the medium or directly translocated into target cells. During bacterial antagonistic encounters, several cellular components important for life become a weak spot prone to an attack. Nucleic acids and the machinery responsible for their synthesis are well conserved across the tree of life. These molecules are part of the information flow in the central dogma of molecular biology and mediate long- and short-term storage for genetic information. The aim of this review is to summarize the diversity of antibacterial molecules that target nucleic acids during antagonistic interbacterial encounters and discuss their potential to promote the emergence antibiotic resistance.

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A DNase Type VI Secretion System Effector Requires Its MIX Domain for Secretion

Abstract: Specialized protein delivery systems are used during bacterial competition to deploy cocktails of toxins that target conserved cellular components. Although numerous toxins have been revealed, the activity of many remains unknown.

Cited by 10 publications

References 60 publications

Agrobacteria deploy two classes of His-Me finger superfamily nuclease effectors exerting different antibacterial capacities against specific bacterial competitors

Agrobacteria deploy two classes of His-Me finger superfamily nuclease effectors exerting different antibacterial capacities against specific bacterial competitors

Recruitment of heterologous substrates by bacterial secretion systems for transkingdom translocation

Intercepting biological messages: Antibacterial molecules targeting nucleic acids during interbacterial conflicts

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