Rhs proteins from diverse bacteria mediate intercellular competition

Koskiniemi, Sanna; Lamoureux, James; Nikolakakis, Kiel; Roodenbeke, Claire T'Kint de; Kaplan, Michael; Low, David A.; Hayes, Christopher S.

doi:10.1073/pnas.1300627110

Cited by 371 publications

(470 citation statements)

References 36 publications

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“…rearrangement hotspot (Rhs) repeat protein. Rhs and related YDrepeat proteins deliver toxic nuclease domains into both Gramnegative and Gram-positive bacteria (32,33). Further, the Ntox28 homolog from Geobacillus sp.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the essential role of CysK in CDI toxin activation

Johnson

Beck

Morse

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Contact-dependent growth inhibition (CDI) is a widespread mechanism of bacterial competition. CDI + bacteria deliver the toxic C-terminal region of contact-dependent inhibition A proteins (CdiA-CT) into neighboring target bacteria and produce CDI immunity proteins (CdiI) to protect against self-inhibition. The CdiA-CT EC536 deployed by uropathogenic Escherichia coli 536 (EC536) is a bacterial toxin 28 (Ntox28) domain that only exhibits ribonuclease activity when bound to the cysteine biosynthetic enzyme O-acetylserine sulfhydrylase A (CysK). Here, we present crystal structures of the CysK/CdiA-CT EC536 binary complex and the neutralized ternary complex of CysK/CdiA-CT/ CdiI EC536 . CdiA-CT EC536 inserts its C-terminal Gly-Tyr-Gly-Ile peptide tail into the active-site cleft of CysK to anchor the interaction. Remarkably, E. coli serine O-acetyltransferase uses a similar Gly-Asp-Gly-Ile motif to form the "cysteine synthase" complex with CysK. The cysteine synthase complex is found throughout bacteria, protozoa, and plants, indicating that CdiA-CT EC536 exploits a highly conserved protein-protein interaction to promote its toxicity. CysK significantly increases CdiA-CT EC536 thermostability and is required for toxin interaction with tRNA substrates. These observations suggest that CysK stabilizes the toxin fold, thereby organizing the nuclease active site for substrate recognition and catalysis. By contrast, Ntox28 domains from Gram-positive bacteria lack C-terminal Gly-Tyr-Gly-Ile motifs, suggesting that they do not interact with CysK. We show that the Ntox28 domain from Ruminococcus lactaris is significantly more thermostable than CdiA-CT EC536 , and its intrinsic tRNA-binding properties support CysK-independent nuclease activity. The striking differences between related Ntox28 domains suggest that CDI toxins may be under evolutionary pressure to maintain low global stability.bacterial competition | structural biology | toxin chaperone | tRNase activity

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Section: Discussionmentioning

confidence: 99%

Unraveling the essential role of CysK in CDI toxin activation

Johnson

Beck

Morse

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, CDI systems may enforce cooperation among surface-associated bacteria by inhibiting the growth of cheaters that lack cognate immunity proteins (703). Genomes of many Alpha-, Beta-, and Gammaproteobacteria, including marine species, harbor the genes that encode CDI systems (707)(708)(709), which may be prevalent in marine surface-associated microbial communities.…”

Section: Deadly Competition: Chemical Agents Predation and Specialimentioning

confidence: 99%

Microbial Surface Colonization and Biofilm Development in Marine Environments

Dang

Lovell

2016

Microbiol Mol Biol Rev

870

636

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SUMMARYBiotic and abiotic surfaces in marine waters are rapidly colonized by microorganisms. Surface colonization and subsequent biofilm formation and development provide numerous advantages to these organisms and support critical ecological and biogeochemical functions in the changing marine environment. Microbial surface association also contributes to deleterious effects such as biofouling, biocorrosion, and the persistence and transmission of harmful or pathogenic microorganisms and their genetic determinants. The processes and mechanisms of colonization as well as key players among the surface-associated microbiota have been studied for several decades. Accumulating evidence indicates that specific cell-surface, cell-cell, and interpopulation interactions shape the composition, structure, spatiotemporal dynamics, and functions of surface-associated microbial communities. Several key microbial processes and mechanisms, including (i) surface, population, and community sensing and signaling, (ii) intraspecies and interspecies communication and interaction, and (iii) the regulatory balance between cooperation and competition, have been identified as critical for the microbial surface association lifestyle. In this review, recent progress in the study of marine microbial surface colonization and biofilm development is synthesized and discussed. Major gaps in our knowledge remain. We pose questions for targeted investigation of surface-specific community-level microbial features, answers to which would advance our understanding of surface-associated microbial community ecology and the biogeochemical functions of these communities at levels from molecular mechanistic details through systems biological integration.

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“…A number of T6SS-secreted effectors were recently found to have contact-dependent antibacterial activity in various bacteria (1). The biochemical functions of characterized effectors include the cell wall-degrading enzymes (2-5), nuclease (6)(7)(8), and membrane lipid-degrading phospholipase (9)(10)(11). These diverse toxin effectors are widespread superfamilies in the bacterial kingdom and therefore likely have a general antibacterial strategy against competitor bacterial cells.…”

mentioning

confidence: 99%

“…Importantly, genes encoding known or putative effectors are often found adjacent to or near vgrG (1,6,7,10) and the requirement of the cognate vgrG for specific type VI toxin-mediated interbacterial competition was demonstrated in Pseudomonas aeruginosa and Enterobacter cloacae…”

mentioning

confidence: 99%

VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor–effector complex

Bondage

Lin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

147

273

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Type VI secretion system (T6SS) is a macromolecular machine used by many Gram-negative bacteria to inject effectors/toxins into eukaryotic hosts or prokaryotic competitors for survival and fitness. To date, our knowledge of the molecular determinants and mechanisms underlying the transport of these effectors remains limited. Here, we report that two T6SS encoded valine-glycine repeat protein G (VgrG) paralogs in Agrobacterium tumefaciens C58 specifically control the secretion and interbacterial competition activity of the type VI DNase toxins Tde1 and Tde2. Deletion and domain-swapping analysis identified that the C-terminal extension of VgrG1 specifically confers Tde1 secretion and Tde1-dependent interbacterial competition activity in planta, and the C-terminal variable region of VgrG2 governs this specificity for Tde2. Functional studies of VgrG1 and VgrG2 variants with stepwise deletion of the C terminus revealed that the C-terminal 31 aa (C31) of VgrG1 and 8 aa (C8) of VgrG2 are the molecular determinants specifically required for delivery of each cognate Tde toxin. Further in-depth studies on Tde toxin delivery mechanisms revealed that VgrG1 interacts with the adaptor/chaperone-effector complex (Tap-1-Tde1) in the absence of proline-alanine-alanine-arginine (PAAR) and the VgrG1-PAAR complex forms independent of Tap-1 and Tde1. Importantly, we identified the regions involved in these interactions. Although the entire C31 segment is required for binding with the Tap-1-Tde1 complex, only the first 15 aa of this region are necessary for PAAR binding. These results suggest that the VgrG1 C terminus interacts sequentially or simultaneously with the Tap-1-Tde1 complex and PAAR to govern Tde1 translocation across bacterial membranes and delivery into target cells for antibacterial activity.type VI secretion system | VgrG | DNase effector | interbacterial competition | Agrobacterium tumefaciens

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Rhs proteins from diverse bacteria mediate intercellular competition

Cited by 371 publications

References 36 publications

Unraveling the essential role of CysK in CDI toxin activation

Unraveling the essential role of CysK in CDI toxin activation

Microbial Surface Colonization and Biofilm Development in Marine Environments

VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor–effector complex

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