Abstract
Type VI Secretion System (T6SS) plays significant roles in microbial activities via injecting effectors into adjacent cells or environments. T6SS increasingly gained attention due to its important influence on pathogenesis, microbial competition, etc. T6SS-associated research is explosively expanding on numerous grounds that call for an efficient resource. The SecReT6 version 3 provides comprehensive information on T6SS and the interactions between T6SS and T6SS-related proteins such as T6SS regulators and T6SS effectors. To assist T6SS researches like microbial competition and regulatory mechanisms, SecReT6 v3 developed online tools for detection and analysis of T6SS and T6SS-related proteins and estimation of T6SS-dependent killing risk. We have identified a novel T6SS regulator and T6SS-dependent killing capacity in Acinetobacter baumannii clinical isolates with the aid of SecReT6 v3. 17,212 T6SSs and plentiful T6SS-related proteins in 26,573 bacterial complete genomes were also detected, analyzed and incorporated into the database. The database is freely available at https://bioinfo-mml.sjtu.edu.cn/SecReT6/.
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Allsopp, L.P., Wood, T.E., Howard, S.A., Maggiorelli, F., Nolan, L.M., Wettstadt, S., and Filloux, A. (2017). RsmA and AmrZ orchestrate the assembly of all three type VI secretion systems in Pseudomonas aeruginosa. Proc Natl Acad Sci USA 114, 7707–7712.
Almagro Armenteros, J.J., Tsirigos, K.D., Sønderby, C.K., Petersen, T.N., Winther, O., Brunak, S., von Heijne, G., and Nielsen, H. (2019). SignalP 5.0 improves signal peptide predictions using deep neural networks. Nat Biotechnol 37, 420–423.
An, Y., Wang, J., Li, C., Revote, J., Zhang, Y., Naderer, T., Hayashida, M., Akutsu, T., Webb, G.I., Lithgow, T., et al. (2017). SecretEPDB: a comprehensive web-based resource for secreted effector proteins of the bacterial types III, IV and VI secretion systems. Sci Rep 7, 41031.
Basler, M., Ho, B.T., and Mekalanos, J.J. (2013). Tit-for-tat: type VI secretion system counterattack during bacterial cell-cell interactions. Cell 152, 884–894.
Bernal, P., Furniss, R.C.D., Fecht, S., Leung, R.C.Y., Spiga, L., Mavridou, D.A.I., and Filloux, A. (2021). A novel stabilization mechanism for the type VI secretion system sheath. Proc Natl Acad Sci USA 118, e2008500118.
Böck, D., Medeiros, J.M., Tsao, H.F., Penz, T., Weiss, G.L., Aistleitner, K., Horn, M., and Pilhofer, M. (2017). In situ architecture, function, and evolution of a contractile injection system. Science 357, 713–717.
Bodenhofer, U., Bonatesta, E., Horejš-Kainrath, C., and Hochreiter, S. (2015). msa: an R package for multiple sequence alignment. Bioinformatics 31, btv494.
Bondage, D.D., Lin, J.S., Ma, L.S., Kuo, C.H., and Lai, E.M. (2016). VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor-effector complex. Proc Natl Acad Sci USA 113, E3931–E3940.
Borgeaud, S., Metzger, L.C., Scrignari, T., and Blokesch, M. (2015). The type VI secretion system of Vibrio cholerae fosters horizontal gene transfer. Science 347, 63–67.
Burkinshaw, B.J., Liang, X., Wong, M., Le, A.N.H., Lam, L., and Dong, T. G. (2018). A type VI secretion system effector delivery mechanism dependent on PAAR and a chaperone-co-chaperone complex. Nat Microbiol 3, 632–640.
Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., and Madden, T.L. (2009). BLAST+: architecture and applications. BMC BioInf 10, 421.
Chen, L., Zou, Y., She, P., and Wu, Y. (2015). Composition, function, and regulation of T6SS in Pseudomonas aeruginosa. Microbiol Res 172, 19–25.
Coyne, M.J., and Comstock, L.E. (2019). Type VI secretion systems and the gut microbiota. Microbiol Spectr 7, PSIB-0009-2018.
Eichinger, V., Nussbaumer, T., Platzer, A., Jehl, M.A., Arnold, R., and Rattei, T. (2016). EffectiveDB—updates and novel features for a better annotation of bacterial secreted proteins and Type III, IV, VI secretion systems. Nucleic Acids Res 44, D669–D674.
Finn, R.D., Clements, J., and Eddy, S.R. (2011). HMMER web server: interactive sequence similarity searching. Nucleic Acids Res 39, W29–W37.
Fridman, C.M., Keppel, K., Gerlic, M., Bosis, E., and Salomon, D. (2020). A comparative genomics methodology reveals a widespread family of membrane-disrupting T6SS effectors. Nat Commun 11, 1085.
Fu, Y., Ho, B.T., and Mekalanos, J.J. (2018). Tracking Vibrio cholerae cell-cell interactions during infection reveals bacterial population dynamics within intestinal microenvironments. Cell Host Microbe 23, 274–281.e2.
Hersch, S.J., Watanabe, N., Stietz, M.S., Manera, K., Kamal, F., Burkinshaw, B., Lam, L., Pun, A., Li, M., Savchenko, A., et al. (2020). Envelope stress responses defend against type six secretion system attacks independently of immunity proteins. Nat Microbiol 5, 706–714.
Ho, B.T., Basler, M., and Mekalanos, J.J. (2013). Type 6 secretion systemmediated immunity to type 4 secretion system-mediated gene transfer. Science 342, 250–253.
Joshi, A., Kostiuk, B., Rogers, A., Teschler, J., Pukatzki, S., and Yildiz, F. H. (2017). Rules of engagement: the type VI secretion system in Vibrio cholerae. Trends Microbiol 25, 267–279.
Jurėnas, D., and Journet, L. (2021). Activity, delivery, and diversity of Type VI secretion effectors. Mol Microbiol 115, 383–394.
Katoh, K., and Standley, D.M. (2013). MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 30, 772–780.
Krogh, A., Larsson, B., von Heijne, G., and Sonnhammer, E.L.L. (2001). Predicting transmembrane protein topology with a hidden markov model: application to complete genomes. J Mol Biol 305, 567–580.
Le, N.H., Pinedo, V., Lopez, J., Cava, F., and Feldman, M.F. (2021). Killing of Gram-negative and Gram-positive bacteria by a bifunctional cell wall-targeting T6SS effector. Proc Natl Acad Sci USA 118, e2106555118.
Li, J., Yao, Y., Xu, H.H., Hao, L., Deng, Z., Rajakumar, K., and Ou, H.Y. (2015). SecReT6: a web-based resource for type VI secretion systems found in bacteria. Environ Microbiol 17, 2196–2202.
Liang, X., Moore, R., Wilton, M., Wong, M.J.Q., Lam, L., and Dong, T.G. (2015). Identification of divergent type VI secretion effectors using a conserved chaperone domain. Proc Natl Acad Sci USA 112, 9106–9111.
Lin, H.H., Filloux, A., and Lai, E.M. (2020). Role of recipient susceptibility factors during contact-dependent interbacterial competition. Front Microbiol 11, 603652.
Medema, M.H., Takano, E., and Breitling, R. (2013). Detecting sequence homology at the gene cluster level with MultiGeneBlast. Mol Biol Evol 30, 1218–1223.
Mok, B.Y., de Moraes, M.H., Zeng, J., Bosch, D.E., Kotrys, A.V., Raguram, A., Hsu, F.S., Radey, M.C., Peterson, S.B., Mootha, V.K., et al. (2020). A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature 583, 631–637.
Price, M.N., Dehal, P.S., and Arkin, A.P. (2010). FastTree 2—approximately maximum-likelihood trees for large alignments. PLoS ONE 5, e9490.
Quentin, D., Ahmad, S., Shanthamoorthy, P., Mougous, J.D., Whitney, J.C., and Raunser, S. (2018). Mechanism of loading and translocation of type VI secretion system effector Tse6. Nat Microbiol 3, 1142–1152.
Russell, A.B., Wexler, A.G., Harding, B.N., Whitney, J.C., Bohn, A.J., Goo, Y.A., Tran, B.Q., Barry, N.A., Zheng, H., Peterson, S.B., et al. (2014). A type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism. Cell Host Microbe 16, 227–236.
Si, M., Zhao, C., Burkinshaw, B., Zhang, B., Wei, D., Wang, Y., Dong, T. G., and Shen, X. (2017). Manganese scavenging and oxidative stress response mediated by type VI secretion system in Burkholderia thailandensis. Proc Natl Acad Sci USA 114, E2233–E2242.
Sievers, F., and Higgins, D.G. (2018). Clustal Omega for making accurate alignments of many protein sequences. Protein Sci 27, 135–145.
Storey, D., McNally, A., Åstrand, M., Sa-Pessoa Graca Santos, J., Rodriguez-Escudero, I., Elmore, B., Palacios, L., Marshall, H., Hobley, L., Molina, M., et al. (2020). Klebsiella pneumoniae type VI secretion system-mediated microbial competition is PhoPQ controlled and reactive oxygen species dependent. PLoS Pathog 16, e1007969.
Sullivan, M.J., Petty, N.K., and Beatson, S.A. (2011). Easyfig: a genome comparison visualizer. Bioinformatics 27, 1009–1010.
Vettiger, A., Winter, J., Lin, L., and Basler, M. (2017). The type VI secretion system sheath assembles at the end distal from the membrane anchor. Nat Commun 8, 16088.
Wang, J., Brodmann, M., and Basler, M. (2019a). Assembly and subcellular localization of bacterial type VI secretion systems. Annu Rev Microbiol 73, 621–638.
Wang, J., Li, J., Hou, Y., Dai, W., Xie, R., Marquez-Lago, T.T., Leier, A., Zhou, T., Torres, V., Hay, I., et al. (2021). BastionHub: a universal platform for integrating and analyzing substrates secreted by Gram-negative bacteria. Nucleic Acids Res 49, D651–D659.
Wang, J., Yang, B., Leier, A., Marquez-Lago, T.T., Hayashida, M., Rocker, A., Zhang, Y., Akutsu, T., Chou, K.C., Strugnell, R.A., et al. (2018). Bastion6: a bioinformatics approach for accurate prediction of type VI secreted effectors. Bioinformatics 34, 2546–2555.
Wang, Y., Wang, Z., Chen, Y., Hua, X., Yu, Y., and Ji, Q. (2019b). A highly efficient CRISPR-Cas9-based genome engineering platform in Acinetobacter baumannii to understand the H2O2-sensing mechanism of OxyR. Cell Chem Biol 26, 1732–1742.e5.
Weber, B.S., Hennon, S.W., Wright, M.S., Scott, N.E., de Berardinis, V., Foster, L.J., Ayala, J.A., Adams, M.D., and Feldman, M.F. (2016). Genetic dissection of the type VI secretion system in Acinetobacter and identification of a novel peptidoglycan hydrolase, TagX, required for its biogenesis. mBio 7, e01253–16.
Yadav, S.K., Magotra, A., Ghosh, S., Krishnan, A., Pradhan, A., Kumar, R., Das, J., Sharma, M., and Jha, G. (2021). Immunity proteins of dual nuclease T6SS effectors function as transcriptional repressors. EMBO Rep 22, e53112.
Yu, G., Lam, T.T.Y., Zhu, H., and Guan, Y. (2018). Two methods for mapping and visualizing associated data on phylogeny using Ggtree. Mol Biol Evol 35, 3041–3043.
Zhao, W., Caro, F., Robins, W., and Mekalanos, J.J. (2018). Antagonism toward the intestinal microbiota and its effect on Vibrio cholerae virulence. Science 359, 210–213.
Zhu, L., Xu, L., Wang, C., Li, C., Li, M., Liu, Q., Wang, X., Yang, W., Pan, D., Hu, L., et al. (2021). T6SS translocates a micropeptide to suppress STING-mediated innate immunity by sequestering manganese. Proc Natl Acad Sci USA 118, e2103526118.
Acknowledgements
This work was supported by the Science and Technology Commission of Shanghai Municipality (19430750600, 19JC1413000), the National Natural Science Foundation of China (31670074), the Medical Excellence Award Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University (XK2019025), and the Science Fund of the Republic of Serbia (7750294, q-bioBDS). We are grateful to Quanjiang Ji at ShanghaiTech University for giving the gene-editing system of pCasAb for A. baumannii.
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Zhang, J., Guan, J., Wang, M. et al. SecReT6 update: a comprehensive resource of bacterial Type VI Secretion Systems. Sci. China Life Sci. 66, 626–634 (2023). https://doi.org/10.1007/s11427-022-2172-x
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DOI: https://doi.org/10.1007/s11427-022-2172-x