Comparative genomics of the type VI secretion systems of Pantoea and Erwinia species reveals the presence of putative effector islands that may be translocated by the VgrG and Hcp proteins

Maayer, Pieter De; Venter, Stephanus N.; Kamber, Tim; Duffy, Brion; Coutinho, Teresa A.; Smits, Theo H. M.

doi:10.1186/1471-2164-12-576

Cited by 83 publications

(110 citation statements)

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“…Commonly, these 'orphan' hcp and vgrG genes are always encoded in the proximity of putative effector genes. 30,31 Further studies demonstrated that in T6SS-dependent delivery, the antibacterial effectors are loaded onto the secretion complex by interaction with PAAR/VgrG or by binding to the inner surface of the Hcp tube. 3 Notably, some VgrG and PAAR proteins can carry antibacterial extension domains, thus acting as secreted T6SS effectors.…”

Section: Nad (P)mentioning

confidence: 99%

“…31,32 The VgrG and PAAR proteins have been demonstrated to carry diverse C-terminal extension domains functioning as T6SS antibacterial effectors, 6,16,32 while the toxic domains fused to Hcp proteins have never been verified to mediate interbacterial antagonism. Our comparative genomics analysis identified an extended Hcp with a C-terminal HNH-DNase toxin domain (ET-toxin) in human O104 Shiga toxin-producing E. coli (STEC) strain C227-11 and piglet diarrhea isolate STEC004 (Fig.…”

Section: A C-terminal Toxin Domain Carried By An Extended Hcp Exhibitmentioning

confidence: 99%

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The Hcp proteins fused with diverse extended-toxin domains represent a novel pattern of antibacterial effectors in type VI secretion systems

et al. 2017

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The type VI secretion system (T6SS) is a widespread molecular weapon deployed by many bacterial species to target eukaryotic host cells or rival bacteria. Using a dynamic injection mechanism, diverse effectors can be delivered by T6SS directly into recipient cells. Here, we report a new family of T6SS effectors encoded by extended Hcps carrying diverse toxin domains. Bioinformatic analyses revealed that these Hcps with C-terminal extension toxins, designated as Hcp-ET, exist widely in the Enterobacteriaceae. To verify our findings, Hcp-ET1 was tested for its antibacterial effect, and showed effective inhibition of target cell growth via the predicted HNH-DNase activity by T6SS-dependent delivery. Further studies showed that Hcp-ET2 mediated interbacterial antagonism via a Tle1 phospholipase (encoded by DUF2235 domain) activity. Notably, comprehensive analyses of protein homology and genomic neighborhoods revealed that Hcp-ET3-4 is fused with 2 toxin domains (Pyocin S3 and Colicin-DNase) C-terminally, and its encoding gene is followed 3 duplications of the cognate immunity genes. However, some bacteria encode a separated hcp-et3 and an orphan et4 (et4 O1 ) genes caused by a terminationcodon mutation in the fusion region between Pyocin S3 and Colicin-DNase encoding fragments. Our results demonstrated that both of these toxins had antibacterial effects. Further, all duplications of the cognate immunity protein contributed to neutralize the DNase toxicity of Pyocin S3 and Colicin, which has not been reported previously. In conclusion, we propose that Hcp-ET proteins are polymorphic T6SS effectors, and thus present a novel encoding pattern of T6SS effectors.

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Section: Nad (P)mentioning

confidence: 99%

Section: A C-terminal Toxin Domain Carried By An Extended Hcp Exhibitmentioning

confidence: 99%

The Hcp proteins fused with diverse extended-toxin domains represent a novel pattern of antibacterial effectors in type VI secretion systems

et al. 2017

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“…Comparative genomic analysis of Pantoea species have demonstrated the presence of up to three gene clusters, designated T6SS-1 through T6SS-3, encoding components of the T6SS (De Maayer et al 2011). Subsequent comparative genomics of sequenced P. ananatis strains indicated that the T6SS-1 and T6SS-3 gene clusters are present in all strains analyzed, whereas the T6SS-2 gene cluster is present in some but not all of these strains (Shyntum et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Pantoea ananatis Utilizes a Type VI Secretion System for Pathogenesis and Bacterial Competition

Shyntum

Theron²,

Venter

et al. 2015

MPMI

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Type VI secretion systems (T6SSs) are a class of macromolecular machines that are recognized as an important virulence mechanism in several Gram-negative bacteria. The genome of Pantoea ananatis LMG 2665 T , a pathogen of pineapple fruit and onion plants, carries two gene clusters whose predicted products have homology with T6SS-associated gene products from other bacteria. Nothing is known regarding the role of these T6SS-1 and T6SS-3 gene clusters in the biology of P. ananatis. Here, we present evidence that T6SS-1 plays an important role in the pathogenicity of P. ananatis LMG 2665T in onion plants, while a strain lacking T6SS-3 remains as pathogenic as the wild-type strain. We also investigated the role of the T6SS-1 system in bacterial competition, the results of which indicated that several bacteria compete less efficiently against wild-type LMG 2665 T than a strain lacking T6SS-1. Additionally, we demonstrated that these phenotypes of strain LMG 2665 T were reliant on the core T6SS products TssA and TssD (Hcp), thus indicating that the T6SS-1 gene cluster encodes a functioning T6SS. Collectively, our data provides the first evidence demonstrating that the T6SS-1 system is a virulence determinant of P. ananatis LMG 2665 T and plays a role in bacterial competition.

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“…Thus, the coordinated functions of VipA, VipB, and ClpV are needed for active secretion. In most T6SSs, hemolysin-coregulated protein (Hcp) and valine-glycine repeat protein G (VgrG) are exported by the secretion machinery, but most likely numerous other proteins are secreted as well (30)(31)(32)(33)(34)(35)(36). The well-characterized Hcp protein is not only secreted but also suggested to be a chaperone that binds to cognate T6SS effector molecules, and it forms a hexameric pore that is required for secretion of diverse effectors encompassing several enzymatic classes (37)(38)(39).…”

mentioning

confidence: 99%

Screening for Inhibition of Vibrio cholerae VipA-VipB Interaction Identifies Small-Molecule Compounds Active against Type VI Secretion

Sun

Bröms

Lavander

et al. 2014

Antimicrob Agents Chemother

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bThe type VI secretion system (T6SS) is the most prevalent bacterial secretion system and an important virulence mechanism utilized by Gram-negative bacteria, either to target eukaryotic cells or to combat other microbes. The components show much variability, but some appear essential for the function, and two homologues, denoted VipA and VipB in Vibrio cholerae, have been identified in all T6SSs described so far. Secretion is dependent on binding of an ␣-helical region of VipA to VipB, and in the absence of this binding, both components are degraded within minutes and secretion is ceased. The aim of the study was to investigate if this interaction could be blocked, and we hypothesized that such inhibition would lead to abrogation of T6S. A library of 9,600 small-molecule compounds was screened for their ability to block the binding of VipA-VipB in a bacterial two-hybrid system (B2H). After excluding compounds that showed cytotoxicity toward eukaryotic cells, that inhibited growth of Vibrio, or that inhibited an unrelated B2H interaction, 34 compounds were further investigated for effects on the T6SS-dependent secretion of hemolysin-coregulated protein (Hcp) or of phospholipase A 1 activity. Two compounds, KS100 and KS200, showed intermediate or strong effects in both assays. Analogues were obtained, and compounds with potent inhibitory effects in the assays and desirable physicochemical properties as predicted by in silico analysis were identified. Since the compounds specifically target a virulence mechanism without affecting bacterial replication, they have the potential to mitigate the virulence with minimal risk for development of resistance.

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Comparative genomics of the type VI secretion systems of Pantoea and Erwinia species reveals the presence of putative effector islands that may be translocated by the VgrG and Hcp proteins

Cited by 83 publications

References 53 publications

The Hcp proteins fused with diverse extended-toxin domains represent a novel pattern of antibacterial effectors in type VI secretion systems

The Hcp proteins fused with diverse extended-toxin domains represent a novel pattern of antibacterial effectors in type VI secretion systems

Pantoea ananatis Utilizes a Type VI Secretion System for Pathogenesis and Bacterial Competition

Screening for Inhibition of Vibrio cholerae VipA-VipB Interaction Identifies Small-Molecule Compounds Active against Type VI Secretion

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