Structural Insights on the Bacteriolytic and Self-protection Mechanism of Muramidase Effector Tse3 in Pseudomonas aeruginosa

Li, Lianbo; Zhang, Weili; Liu, Qisong; Gao, Ying; Wang, Yun; Wang, David Zhigang; Li, Zigang; Wang, Tao

doi:10.1074/jbc.c113.506097

Cited by 26 publications

(22 citation statements)

References 42 publications

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“…Indeed, with the exception of Tse3, all effectors shown to interact with Hcp are under 20 kDa and thus near the expected molecular weight cut‐off for a globular protein bound to the ∼ 40 Å internal pore of the Hcp hexamer (Zheng and Leung, ; Chou et al ., ; Lin et al ., ; Silverman et al ., ). At 44 kDa, Tse3 is considerably above this cut‐off; however, the recent determination of its crystal structure reveals an elongated fold that could also be accommodated within Hcp ring(s) (Li et al ., ; Wang et al ., ). In contrast, bioinformatic data suggest that most VgrG‐associated effectors are in excess of 60 kDa (Russell et al ., ).…”

Section: Discussionmentioning

confidence: 99%

Genetically distinct pathways guide effector export through the type VI secretion system

Whitney

Beck

Goo

et al. 2014

Molecular Microbiology

179

251

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Summary Bacterial secretion systems often employ molecular chaperones to recognize and facilitate export of their substrates. Recent work demonstrated that a secreted component of the type VI secretion system (T6SS), hemolysin co-regulated protein (Hcp), binds directly to effectors, enhancing their stability in the bacterial cytoplasm. Herein, we describe a quantitative cellular proteomics screen for T6S substrates that exploits this chaperone-like quality of Hcp. Application of this approach to the Hcp secretion island I-encoded T6SS (H1-T6SS) of Pseudomonas aeruginosa led to the identification of a novel effector protein, termed Tse4 (type VI secretion exported 4), subsequently shown to act as a potent intra-specific H1-T6SS-delivered antibacterial toxin. Interestingly, our screen failed to identify two predicted H1-T6SS effectors, Tse5 and Tse6, which differ from Hcp-stabilized substrates by the presence of toxin-associated PAAR-repeat motifs and genetic linkage to members of the valine-glycine repeat protein G (vgrG) genes. Genetic studies further distinguished these two groups of effectors: Hcp-stabilized effectors were found to display redundancy in interbacterial competition with respect to the requirement for the two H1-T6SS-exported VgrG proteins, whereas Tse5 and Tse6 delivery strictly required a cognate VgrG. Together, we propose that interaction with either VgrG or Hcp defines distinct pathways for T6S effector export.

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Section: Discussionmentioning

confidence: 99%

Genetically distinct pathways guide effector export through the type VI secretion system

Whitney

Beck

Goo

et al. 2014

Molecular Microbiology

179

251

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“…9) occur as a heterotetramer of two Tae4 molecules and a Tai4 dimer (Benz et al, 2013;Zhang et al, 2013). Tse3 that anchors to the target membrane in a calcium-dependent way (Lu et al, 2014), adopts a goose-type lysozyme-like structure and acts as a muramidase that cleaves the b-1,4 bond between N-acetylmuramic acid (MurNAc) and Nacetylglucosamine (GlcNAc) in peptidoglycan (Li et al, 2013b;Lu et al, 2013;Wang et al, 2013). In P. protegens Pf-5, a peptidoglycan glycoside hydrolase effector not orthologous to Tse3 was identified via an informatics search and characterized.…”

Section: Toxic Effectors and Immunity Proteins Of T6sssmentioning

confidence: 99%

Ribosomally encoded antibacterial proteins and peptides fromPseudomonas

2014

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Members of the Pseudomonas genus produce diverse secondary metabolites affecting other bacteria, fungi or predating nematodes and protozoa but are also equipped with the capacity to secrete different types of ribosomally encoded toxic peptides and proteins, ranging from small microcins to large tailocins. Studies with the human pathogen Pseudomonas aeruginosa have revealed that effector proteins of type VI secretion systems are part of the antibacterial armamentarium deployed by pseudomonads. A novel class of antibacterial proteins with structural similarity to plant lectins was discovered by studying antagonism among plant-associated Pseudomonas strains. A genomic perspective on pseudomonad bacteriocinogeny shows that the modular architecture of S pyocins of P. aeruginosa is retained in a large diversified group of bacteriocins, most of which target DNA or RNA. Similar modularity is present in as yet poorly characterized Rhs (recombination hot spot) proteins and CDI (contact-dependent inhibition) proteins. Well-delimited domains for receptor recognition or cytotoxicity enable the design of chimeric toxins with novel functionalities, which has been applied successfully for S and R pyocins. Little is known regarding how these antibacterials are released and ultimately reach their targets. Other remaining issues concern the identification of environmental triggers activating these systems and assessment of their ecological impact in niches populated by pseudomonads.

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“…The β1,4 bonds between muramic acid and N-acetylglucosamine are common targets of a multitude of bacteriocidal enzymes, including lysozyme. Indeed, these enzymes share the lysozyme muramidase fold, but have an active site tyrosine residue and exhibit N -acetylglucosaminidase activity (6, 65). The VgrG protein of the puncturing device can also exhibit peptidoglycan degrading activity.…”

Section: T6ss Effectorsmentioning

confidence: 99%

The Versatile Type VI Secretion System

Alteri

Mobley

2016

Microbiol Spectr

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Summary Bacterial Type VI Secretion Systems (T6SS) function as contractile nanomachines to puncture target cells and deliver lethal effectors. In the ten years since the discovery of the T6SS, much has been learned about the structure and function of this versatile protein secretion apparatus. Most of the conserved protein components that comprise the T6SS apparatus itself have been identified and ascribed specific functions. In addition, numerous effector proteins that are translocated by the T6SS have been identified and characterized. These protein effectors usually represent toxic cargoes that are delivered by the attacker cell to a target cell. The field is beginning to better understand the lifestyle or physiology that dictates when bacteria normally express their T6SS. In this Chapter, we consider what is known about the structure and regulation of the T6SS, the numerous classes of antibacterial effector T6SS substrates, and how the action of the T6SS relates to a given lifestyle or behavior in certain bacteria.

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Structural Insights on the Bacteriolytic and Self-protection Mechanism of Muramidase Effector Tse3 in Pseudomonas aeruginosa

Cited by 26 publications

References 42 publications

Genetically distinct pathways guide effector export through the type VI secretion system

Genetically distinct pathways guide effector export through the type VI secretion system

Ribosomally encoded antibacterial proteins and peptides fromPseudomonas

The Versatile Type VI Secretion System

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