Structural and functional diversity of type IV secretion systems.
Journal
Nature reviews. Microbiology
ISSN: 1740-1534
Titre abrégé: Nat Rev Microbiol
Pays: England
ID NLM: 101190261
Informations de publication
Date de publication:
09 Oct 2023
09 Oct 2023
Historique:
accepted:
13
09
2023
medline:
10
10
2023
pubmed:
10
10
2023
entrez:
9
10
2023
Statut:
aheadofprint
Résumé
Considerable progress has been made in recent years in the structural and molecular biology of type IV secretion systems in Gram-negative bacteria. The latest advances have substantially improved our understanding of the mechanisms underlying the recruitment and delivery of DNA and protein substrates to the extracellular environment or target cells. In this Review, we aim to summarize these exciting structural and molecular biology findings and to discuss their functional implications for substrate recognition, recruitment and translocation, as well as the biogenesis of extracellular pili. We also describe adaptations necessary for deploying a breadth of processes, such as bacterial survival, host-pathogen interactions and biotic and abiotic adhesion. We highlight the functional and structural diversity that allows this extremely versatile secretion superfamily to function under different environmental conditions and in different bacterial species. Additionally, we emphasize the importance of further understanding the mechanism of type IV secretion, which will support us in combating antimicrobial resistance and treating type IV secretion system-related infections.
Identifiants
pubmed: 37814112
doi: 10.1038/s41579-023-00974-3
pii: 10.1038/s41579-023-00974-3
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. Crown.
Références
Alvarez-Martinez, C. E. & Christie, P. J. Biological diversity of prokaryotic type IV secretion systems. Microbiol. Mol. Biol. Rev. 73, 775–808 (2009).
pubmed: 19946141
pmcid: 2786583
doi: 10.1128/MMBR.00023-09
Cascales, E. & Christie, P. J. The versatile bacterial type IV secretion systems. Nat. Rev. Microbiol. 1, 137–149 (2003).
pubmed: 15035043
doi: 10.1038/nrmicro753
Costa, T. R. et al. Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nat. Rev. Microbiol. 13, 343–359 (2015).
pubmed: 25978706
doi: 10.1038/nrmicro3456
Christie, P. J. The mosaic type IV secretion systems. EcoSal Plus https://doi.org/10.1128/ecosalplus.ESP-0020-2015 (2016).
Waksman, G. From conjugation to T4S systems in Gram-negative bacteria: a mechanistic biology perspective. EMBO Rep. 20, e47012 (2019).
pubmed: 30602585
pmcid: 6362355
doi: 10.15252/embr.201847012
Cabezon, E., de la Cruz, F. & Arechaga, I. Conjugation inhibitors and their potential use to prevent dissemination of antibiotic resistance genes in bacteria. Front. Microbiol. 8, 2329 (2017).
pubmed: 29255449
pmcid: 5723004
doi: 10.3389/fmicb.2017.02329
Boudaher, E. & Shaffer, C. L. Inhibiting bacterial secretion systems in the fight against antibiotic resistance. MedChemComm 10, 682–692 (2019).
pubmed: 31741728
pmcid: 6677025
doi: 10.1039/C9MD00076C
Christie, P. J., Atmakuri, K., Krishnamoorthy, V., Jakubowski, S. & Cascales, E. Biogenesis, architecture, and function of bacterial type IV secretion systems. Annu. Rev. Microbiol. 59, 451–485 (2005).
pubmed: 16153176
doi: 10.1146/annurev.micro.58.030603.123630
Cabezón, E., Ripoll-Rozada, J., Peña, A., de la Cruz, F. & Arechaga, I. Towards an integrated model of bacterial conjugation. FEMS Microbiol. Rev. 39, 81–95 (2015).
pubmed: 25154632
Costa, T. R. D. et al. Type IV secretion systems: advances in structure, function, and activation. Mol. Microbiol. 115, 436–452 (2021).
pubmed: 33326642
pmcid: 8026593
doi: 10.1111/mmi.14670
Sheedlo, M. J., Ohi, M. D., Lacy, D. B. & Cover, T. L. Molecular architecture of bacterial type IV secretion systems. PLoS Pathog. 18, e1010720 (2022).
pubmed: 35951533
pmcid: 9371333
doi: 10.1371/journal.ppat.1010720
Sgro, G. G. et al. Bacteria-killing type IV secretion systems. Front. Microbiol. 10, 1078 (2019).
pubmed: 31164878
pmcid: 6536674
doi: 10.3389/fmicb.2019.01078
Gonzalez-Rivera, C., Bhatty, M. & Christie, P. J. Mechanism and function of type IV secretion during infection of the human host. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.VMBF-0024-2015 (2016).
Macé, K. et al. Cryo-EM structure of a type IV secretion system. Nature 607, 191–196 (2022). The study reports high-resolution atomic structure of a nearly complete T4SS, representing a significant leap forward in the understanding of type IV secretion, as it reveals crucial details of assembly, function and subunit interfaces, opening new possibilities for rational drug design and establishing a workflow for structural determination of these complex machineries.
pubmed: 35732732
pmcid: 9259494
doi: 10.1038/s41586-022-04859-y
Amin, H., Ilangovan, A. & Costa, T. R. D. Architecture of the outer-membrane core complex from a conjugative type IV secretion system. Nat. Commun. 12, 6834 (2021). The study presents the high-resolution structure of the outer membrane core complex from an expanded conjugative T4SS, shedding light on the mechanisms of conjugative pilus outgrowth and DNA translocation during bacterial conjugation, revealing structural adaptations that contribute to the dynamic properties of the machinery.
pubmed: 34824240
pmcid: 8617172
doi: 10.1038/s41467-021-27178-8
Chandran, V. et al. Structure of the outer membrane complex of a type IV secretion system. Nature 462, 1011–1015 (2009).
pubmed: 19946264
pmcid: 2797999
doi: 10.1038/nature08588
Fronzes, R. et al. Structure of a type IV secretion system core complex. Science 323, 266–268 (2009).
pubmed: 19131631
pmcid: 6710095
doi: 10.1126/science.1166101
Rivera-Calzada, A. et al. Structure of a bacterial type IV secretion core complex at subnanometre resolution. EMBO J. 32, 1195–1204 (2013).
pubmed: 23511972
pmcid: 3630358
doi: 10.1038/emboj.2013.58
Low, H. H. et al. Structure of a type IV secretion system. Nature 508, 550–553 (2014).
pubmed: 24670658
pmcid: 3998870
doi: 10.1038/nature13081
Gordon, J. E. et al. Use of chimeric type IV secretion systems to define contributions of outer membrane subassemblies for contact-dependent translocation. Mol. Microbiol. 105, 273–293 (2017).
pubmed: 28452085
pmcid: 5518639
doi: 10.1111/mmi.13700
Sgro, G. G. et al. Cryo-EM structure of the bacteria-killing type IV secretion system core complex from Xanthomonas citri. Nat. Microbiol. 3, 1429–1440 (2018). The paper reports the high-resolution cryo-EM structure of a T4SS involved in bacterial killing, advancing our understanding of the structural similarities and differences among functionally distinct T4SSs.
pubmed: 30349081
pmcid: 6264810
doi: 10.1038/s41564-018-0262-z
Cascales, E., Atmakuri, K., Sarkar, M. K. & Christie, P. J. DNA substrate-induced activation of the Agrobacterium VirB/VirD4 type IV secretion system. J. Bacteriol. 195, 2691–2704 (2013).
pubmed: 23564169
pmcid: 3676061
doi: 10.1128/JB.00114-13
Cascales, E. & Christie, P. J. Agrobacterium VirB10, an ATP energy sensor required for type IV secretion. Proc. Natl Acad. Sci. USA 101, 17228–17233 (2004).
pubmed: 15569944
pmcid: 535377
doi: 10.1073/pnas.0405843101
Banta, L. M. et al. An Agrobacterium VirB10 mutation conferring a type IV secretion system gating defect. J. Bacteriol. 193, 2566–2574 (2011).
pubmed: 21421757
pmcid: 3133169
doi: 10.1128/JB.00038-11
Darbari, V. C. et al. Electrostatic switching controls channel dynamics of the sensor protein VirB10 in A. tumefaciens type IV secretion system. ACS Omega 5, 3271–3281 (2020).
pubmed: 32118142
pmcid: 7045316
doi: 10.1021/acsomega.9b03313
Souza, D. P. et al. A component of the Xanthomonadaceae type IV secretion system combines a VirB7 motif with a N0 domain found in outer membrane transport proteins. PLoS Pathog. 7, e1002031 (2011).
pubmed: 21589901
pmcid: 3093366
doi: 10.1371/journal.ppat.1002031
Nakano, N., Kubori, T., Kinoshita, M., Imada, K. & Nagai, H. Crystal structure of Legionella DotD: insights into the relationship between type IVB and type II/III secretion systems. PLoS Pathog. 6, e1001129 (2010).
pubmed: 20949065
pmcid: 2951367
doi: 10.1371/journal.ppat.1001129
Lockwood, D. C., Amin, H., Costa, T. R. D. & Schroeder, G. N. The Legionella pneumophila Dot/Icm type IV secretion system and its effectors. Microbiology https://doi.org/10.1099/mic.0.001187 (2022).
Aly, K. A. & Baron, C. The VirB5 protein localizes to the T-pilus tips in Agrobacterium tumefaciens. Microbiology 153, 3766–3775 (2007).
pubmed: 17975085
doi: 10.1099/mic.0.2007/010462-0
Jakubowski, S. J., Krishnamoorthy, V., Cascales, E. & Christie, P. J. Agrobacterium tumefaciens VirB6 domains direct the ordered export of a DNA substrate through a type IV secretion system. J. Mol. Biol. 341, 961–977 (2004).
pubmed: 15328612
pmcid: 3918220
doi: 10.1016/j.jmb.2004.06.052
Hospenthal, M. K., Costa, T. R. D. & Waksman, G. A comprehensive guide to pilus biogenesis in Gram-negative bacteria. Nat. Rev. Microbiol. 15, 365–379 (2017).
pubmed: 28496159
doi: 10.1038/nrmicro.2017.40
Backert, S., Fronzes, R. & Waksman, G. VirB2 and VirB5 proteins: specialized adhesins in bacterial type-IV secretion systems? Trends Microbiol. 16, 409–413 (2008).
pubmed: 18706815
doi: 10.1016/j.tim.2008.07.001
Bönig, T., Olbermann, P., Bats, S. H., Fischer, W. & Josenhans, C. Systematic site-directed mutagenesis of the Helicobacter pylori CagL protein of the Cag type IV secretion system identifies novel functional domains. Sci. Rep. 6, 38101 (2016).
pubmed: 27922023
pmcid: 5138618
doi: 10.1038/srep38101
Pham, K. T. et al. CagI is an essential component of the Helicobacter pylori Cag type IV secretion system and forms a complex with CagL. PLoS ONE 7, e35341 (2012).
pubmed: 22493745
pmcid: 3320882
doi: 10.1371/journal.pone.0035341
Khara, P., Song, L., Christie, P. J. & Hu, B. In situ visualization of the pKM101-encoded type IV secretion system reveals a highly symmetric ATPase energy center. mBio 12, e0246521 (2021).
pubmed: 34634937
doi: 10.1128/mBio.02465-21
Liu, X., Khara, P., Baker, M. L., Christie, P. J. & Hu, B. Structure of a type IV secretion system core complex encoded by multi-drug resistance F plasmids. Nat. Commun. 13, 379 (2022).
pubmed: 35046412
pmcid: 8770708
doi: 10.1038/s41467-022-28058-5
Kitao, T., Kubori, T. & Nagai, H. Recent advances in structural studies of the Legionella pneumophila Dot/Icm type IV secretion system. Microbiol. Immunol. 66, 67–74 (2022).
pubmed: 34807482
pmcid: 9302130
doi: 10.1111/1348-0421.12951
Gomez-Valero, L. et al. More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells. Proc. Natl Acad. Sci. USA 116, 2265–2273 (2019).
pubmed: 30659146
pmcid: 6369783
doi: 10.1073/pnas.1808016116
Asrat, S., de Jesus, D. A., Hempstead, A. D., Ramabhadran, V. & Isberg, R. R. Bacterial pathogen manipulation of host membrane trafficking. Annu. Rev. Cell Dev. Biol. 30, 79–109 (2014).
pubmed: 25103867
doi: 10.1146/annurev-cellbio-100913-013439
Durie, C. L. et al. Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complex. eLife 9, e59530 (2020). This study reports high-resolution structure of the L. pneumophila Dot/Icm T4SS, which plays a crucial role in niche establishment and the pathogenesis of Legionnaire’s disease.
pubmed: 32876045
pmcid: 7511231
doi: 10.7554/eLife.59530
Sheedlo, M. J. et al. Cryo-EM reveals new species-specific proteins and symmetry elements in the Legionella pneumophila Dot/Icm T4SS. eLife 10, e70427 (2021).
pubmed: 34519271
pmcid: 8486379
doi: 10.7554/eLife.70427
Varga, M. G. et al. Pathogenic Helicobacter pylori strains translocate DNA and activate TLR9 via the cancer-associated Cag type IV secretion system. Oncogene 35, 6262–6269 (2016).
pubmed: 27157617
pmcid: 5102820
doi: 10.1038/onc.2016.158
Tegtmeyer, N., Neddermann, M., Asche, C. I. & Backert, S. Subversion of host kinases: a key network in cellular signaling hijacked by Helicobacter pylori CagA. Mol. Microbiol. 105, 358–372 (2017).
pubmed: 28508421
doi: 10.1111/mmi.13707
Pfannkuch, L. et al. ADP heptose, a novel pathogen-associated molecular pattern identified in Helicobacter pylori. FASEB J. 33, 9087–9099 (2019).
pubmed: 31075211
pmcid: 6662969
doi: 10.1096/fj.201802555R
Cover, T. L., Lacy, D. B. & Ohi, M. D. The Helicobacter pylori Cag type IV secretion system. Trends Microbiol. 28, 682–695 (2020).
pubmed: 32451226
pmcid: 7363556
doi: 10.1016/j.tim.2020.02.004
Frick-Cheng, A. E. et al. Molecular and structural analysis of the Helicobacter pylori Cag type IV secretion system core complex. mBio 7, e02001–e02015 (2016).
pubmed: 26758182
pmcid: 4725015
doi: 10.1128/mBio.02001-15
Sheedlo, M. J. et al. Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex. eLife 9, e59495 (2020).
pubmed: 32876048
pmcid: 7511236
doi: 10.7554/eLife.59495
Hu, B., Khara, P. & Christie, P. J. Structural bases for F plasmid conjugation and F pilus biogenesis in Escherichia coli. Proc. Natl Acad. Sci. USA 116, 14222–14227 (2019). The study presents in situ cryo-electron tomography visualization of the entire conjugative F T4SS, revealing four distinct conformational states of the machinery, and providing a step-by-step mechanism of bacterial conjugation and pilus outgrowth, along with architectural representations of the machinery in each state.
pubmed: 31239340
pmcid: 6628675
doi: 10.1073/pnas.1904428116
Ghosal, D., Chang, Y. W., Jeong, K. C., Vogel, J. P. & Jensen, G. J. In situ structure of the Legionella Dot/Icm type IV secretion system by electron cryotomography. EMBO Rep. 18, 726–732 (2017). The study reports cryo-electron tomography visualization of the Dot/Icm T4SS in L. pneumophila, revealing a common overall architecture shared across functionally diverse T4SSs.
pubmed: 28336774
pmcid: 5412798
doi: 10.15252/embr.201643598
Chetrit, D., Hu, B., Christie, P. J., Roy, C. R. & Liu, J. A unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretion channel. Nat. Microbiol. 3, 678–686 (2018).
pubmed: 29784975
pmcid: 5970066
doi: 10.1038/s41564-018-0165-z
Park, D., Steiner, S., Shao, M., Roy, C. R. & Liu, J. Developmental transitions coordinate assembly of the Coxiella burnetii Dot/Icm type IV secretion system. Infect. Immun. 90, e0041022 (2022).
pubmed: 36190257
doi: 10.1128/iai.00410-22
Newton, H. J., McDonough, J. A. & Roy, C. R. Effector protein translocation by the Coxiella burnetii Dot/Icm type IV secretion system requires endocytic maturation of the pathogen-occupied vacuole. PLoS ONE 8, e54566 (2013).
pubmed: 23349930
pmcid: 3547880
doi: 10.1371/journal.pone.0054566
Chang, Y. W., Shaffer, C. L., Rettberg, L. A., Ghosal, D. & Jensen, G. J. In vivo structures of the Helicobacter pylori Cag type IV secretion system. Cell Rep. 23, 673–681 (2018).
pubmed: 29669273
pmcid: 5931392
doi: 10.1016/j.celrep.2018.03.085
Hu, B. et al. In situ molecular architecture of the Helicobacter pylori Cag type IV secretion system. mBio https://doi.org/10.1128/mBio.00849-19 (2019).
Chung, J. M. et al. Structure of the Helicobacter pylori Cag type IV secretion system. eLife 8, e47644 (2019). The paper presents the high-resolution structure of the H. pylori Cag T4SS, which is required for H. pylori infection of the human gastrointestinal tract.
pubmed: 31210639
pmcid: 6620104
doi: 10.7554/eLife.47644
Tegtmeyer, N. et al. Toll-like receptor 5 activation by the CagY repeat domains of Helicobacter pylori. Cell Rep. 32, 108159 (2020).
pubmed: 32937132
doi: 10.1016/j.celrep.2020.108159
Audette, G. F., Manchak, J., Beatty, P., Klimke, W. A. & Frost, L. S. Entry exclusion in F-like plasmids requires intact TraG in the donor that recognizes its cognate TraS in the recipient. Microbiology 153, 442–451 (2007).
pubmed: 17259615
doi: 10.1099/mic.0.2006/001917-0
Marrero, J. & Waldor, M. K. Determinants of entry exclusion within Eex and TraG are cytoplasmic. J. Bacteriol. 189, 6469–6473 (2007).
pubmed: 17573467
pmcid: 1951900
doi: 10.1128/JB.00522-07
Gillespie, J. J. et al. An anomalous type IV secretion system in Rickettsia is evolutionarily conserved. PLoS ONE 4, e4833 (2009).
pubmed: 19279686
pmcid: 2653234
doi: 10.1371/journal.pone.0004833
Gillespie, J. J. et al. Phylogenomics reveals a diverse Rickettsiales type IV secretion system. Infect. Immun. 78, 1809–1823 (2010).
pubmed: 20176788
pmcid: 2863512
doi: 10.1128/IAI.01384-09
Rancès, E., Voronin, D., Tran-Van, V. & Mavingui, P. Genetic and functional characterization of the type IV secretion system in Wolbachia. J. Bacteriol. 190, 5020–5030 (2008).
pubmed: 18502862
pmcid: 2447017
doi: 10.1128/JB.00377-08
Nagai, H. & Roy, C. R. The DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporter. EMBO J. 20, 5962–5970 (2001).
pubmed: 11689436
pmcid: 125688
doi: 10.1093/emboj/20.21.5962
Skoog, E. C. et al. CagY-dependent regulation of type IV secretion in Helicobacter pylori is associated with alterations in integrin binding. mBio 9, e00717–e00718 (2018).
pubmed: 29764950
pmcid: 5954226
doi: 10.1128/mBio.00717-18
Aras, R. A., Kang, J., Tschumi, A. I., Harasaki, Y. & Blaser, M. J. Extensive repetitive DNA facilitates prokaryotic genome plasticity. Proc. Natl Acad. Sci. USA 100, 13579–13584 (2003).
pubmed: 14593200
pmcid: 263856
doi: 10.1073/pnas.1735481100
Barrozo, R. M. et al. Functional plasticity in the type IV secretion system of Helicobacter pylori. PLoS Pathog. 9, e1003189 (2013).
pubmed: 23468628
pmcid: 3585145
doi: 10.1371/journal.ppat.1003189
Llosa, M. & Alkorta, I. in Type IV Secretion in Gram-Negative and Gram-Positive Bacteria (eds Backert, S. & Grohmann, E.) 143–168 (Springer International, 2017).
Gomis-Rüth, F. X. et al. The bacterial conjugation protein TrwB resembles ring helicases and F1-ATPase. Nature 409, 637–641 (2001).
pubmed: 11214325
doi: 10.1038/35054586
Whitaker, N. et al. The all-alpha domains of coupling proteins from the Agrobacterium tumefaciens VirB/VirD4 and Enterococcus faecalis pCF10-encoded type IV secretion systems confer specificity to binding of cognate DNA substrates. J. Bacteriol. 197, 2335–2349 (2015).
pubmed: 25939830
pmcid: 4524192
doi: 10.1128/JB.00189-15
Oka, G. U. et al. Structural basis for effector recognition by an antibacterial type IV secretion system. Proc. Natl Acad. Sci. USA 119, e2112529119 (2022).
pubmed: 34983846
doi: 10.1073/pnas.2112529119
Atmakuri, K., Cascales, E. & Christie, P. J. Energetic components VirD4, VirB11 and VirB4 mediate early DNA transfer reactions required for bacterial type IV secretion. Mol. Microbiol. 54, 1199–1211 (2004).
pubmed: 15554962
doi: 10.1111/j.1365-2958.2004.04345.x
Ripoll-Rozada, J., Zunzunegui, S., de la Cruz, F., Arechaga, I. & Cabezon, E. Functional interactions of VirB11 traffic ATPases with VirB4 and VirD4 molecular motors in type IV secretion systems. J. Bacteriol. 195, 4195–4201 (2013).
pubmed: 23852869
pmcid: 3754731
doi: 10.1128/JB.00437-13
Savvides, S. N. et al. VirB11 ATPases are dynamic hexameric assemblies: new insights into bacterial type IV secretion. EMBO J. 22, 1969–1980 (2003).
pubmed: 12727865
pmcid: 156095
doi: 10.1093/emboj/cdg223
Hare, S., Bayliss, R., Baron, C. & Waksman, G. A large domain swap in the VirB11 ATPase of Brucella suis leaves the hexameric assembly intact. J. Mol. Biol. 360, 56–66 (2006).
pubmed: 16730027
doi: 10.1016/j.jmb.2006.04.060
Park, D., Chetrit, D., Hu, B., Roy, C. R. & Liu, J. Analysis of Dot/Icm type IVB secretion system subassemblies by cryoelectron tomography reveals conformational changes induced by DotB binding. mBio 11, e03328–03319 (2020).
pubmed: 32071271
pmcid: 7029142
doi: 10.1128/mBio.03328-19
Sagulenko, E., Sagulenko, V., Chen, J. & Christie, P. J. Role of Agrobacterium VirB11 ATPase in T-pilus assembly and substrate selection. J. Bacteriol. 183, 5813–5825 (2001).
pubmed: 11566978
pmcid: 99657
doi: 10.1128/JB.183.20.5813-5825.2001
Hilleringmann, M. et al. Inhibitors of Helicobacter pylori ATPase Cagα block CagA transport and Cag virulence. Microbiology 152, 2919–2930 (2006).
pubmed: 17005973
doi: 10.1099/mic.0.28984-0
Nagai, H. et al. A C-terminal translocation signal required for Dot/Icm-dependent delivery of the Legionella RalF protein to host cells. Proc. Natl Acad. Sci. USA 102, 826–831 (2005).
pubmed: 15613486
doi: 10.1073/pnas.0406239101
Cambronne, E. D. & Roy, C. R. The Legionella pneumophila IcmSW complex interacts with multiple Dot/Icm effectors to facilitate type IV translocation. PLoS Pathog. 3, e188 (2007).
pubmed: 18069892
pmcid: 2134951
doi: 10.1371/journal.ppat.0030188
Kim, H. et al. Structural basis for effector protein recognition by the Dot/Icm type IVB coupling protein complex. Nat. Commun. 11, 2623 (2020).
pubmed: 32457311
pmcid: 7251119
doi: 10.1038/s41467-020-16397-0
Jeong, K. C., Sutherland, M. C. & Vogel, J. P. Novel export control of a Legionella Dot/Icm substrate is mediated by dual, independent signal sequences. Mol. Microbiol. 96, 175–188 (2015).
pubmed: 25582583
doi: 10.1111/mmi.12928
Meir, A., Chetrit, D., Liu, L., Roy, C. R. & Waksman, G. Legionella DotM structure reveals a role in effector recruiting to the type 4B secretion system. Nat. Commun. 9, 507 (2018). The paper presents the crystallographic structure of DotM, revealing a novel mechanism of effector recognition by the Dot/Icm T4SS in L. pneumophila.
pubmed: 29410427
pmcid: 5802825
doi: 10.1038/s41467-017-02578-x
Mace, K. et al. Proteins DotY and DotZ modulate the dynamics and localization of the type IVB coupling complex of Legionella pneumophila. Mol. Microbiol. 117, 307–319 (2022).
pubmed: 34816517
doi: 10.1111/mmi.14847
Meir, A., Macé, K., Vegunta, Y., Williams, S. M. & Waksman, G. Substrate recruitment mechanism by Gram-negative type III, IV, and VI bacterial injectisomes. Trends Microbiol. 31, 916–932 (2023).
pubmed: 37085348
doi: 10.1016/j.tim.2023.03.005
Kwak, M. J. et al. Architecture of the type IV coupling protein complex of Legionella pneumophila. Nat. Microbiol. 2, 17114 (2017).
pubmed: 28714967
pmcid: 6497169
doi: 10.1038/nmicrobiol.2017.114
Meir, A. et al. Mechanism of effector capture and delivery by the type IV secretion system from Legionella pneumophila. Nat. Commun. 11, 2864 (2020).
pubmed: 32513920
pmcid: 7280309
doi: 10.1038/s41467-020-16681-z
Vincent, C. D., Friedman, J. R., Jeong, K. C., Sutherland, M. C. & Vogel, J. P. Identification of the DotL coupling protein subcomplex of the Legionella Dot/Icm type IV secretion system. Mol. Microbiol. 85, 378–391 (2012).
pubmed: 22694730
pmcid: 3391322
doi: 10.1111/j.1365-2958.2012.08118.x
Xu, J. et al. Structural insights into the roles of the IcmS–IcmW complex in the type IVb secretion system of Legionella pneumophila. Proc. Natl Acad. Sci. USA 114, 13543–13548 (2017).
pubmed: 29203674
pmcid: 5754761
doi: 10.1073/pnas.1706883115
Pattis, I., Weiss, E., Laugks, R., Haas, R. & Fischer, W. The Helicobacter pylori CagF protein is a type IV secretion chaperone-like molecule that binds close to the C-terminal secretion signal of the CagA effector protein. Microbiology 153, 2896–2909 (2007).
pubmed: 17768234
doi: 10.1099/mic.0.2007/007385-0
Wu, X. et al. Mechanism of regulation of the Helicobacter pylori Cagβ ATPase by CagZ. Nat. Commun. 14, 479 (2023).
pubmed: 36717564
pmcid: 9886983
doi: 10.1038/s41467-023-36218-4
de la Cruz, F., Frost, L. S., Meyer, R. J. & Zechner, E. L. Conjugative DNA metabolism in Gram-negative bacteria. FEMS Microbiol. Rev. 34, 18–40 (2010).
pubmed: 19919603
doi: 10.1111/j.1574-6976.2009.00195.x
Ilangovan, A. et al. Cryo-EM structure of a relaxase reveals the molecular basis of DNA unwinding during bacterial conjugation. Cell 169, 708–721.e12 (2017). The study reveals the structure of the relaxase protein, the core component of the relaxosome complex involved in DNA processing prior to conjugation, showing that two distinct activities of the relaxase, the transesterase activity required for DNA nicking and the helicase activity essential for DNA unwinding, are simultaneously performed by two distinct structural conformers.
pubmed: 28457609
pmcid: 5422253
doi: 10.1016/j.cell.2017.04.010
Datta, S., Larkin, C. & Schildbach, J. F. Structural insights into single-stranded DNA binding and cleavage by F factor TraI. Structure 11, 1369–1379 (2003).
pubmed: 14604527
doi: 10.1016/j.str.2003.10.001
Rice, P. A., Yang, S., Mizuuchi, K. & Nash, H. A. Crystal structure of an IHF-DNA complex: a protein-induced DNA U-turn. Cell 87, 1295–1306 (1996).
pubmed: 8980235
doi: 10.1016/S0092-8674(00)81824-3
Luo, Y., Gao, Q. & Deonier, R. C. Mutational and physical analysis of F plasmid traY protein binding to oriT. Mol. Microbiol. 11, 459–469 (1994).
pubmed: 8152370
doi: 10.1111/j.1365-2958.1994.tb00327.x
Lu, J. et al. Structural basis of specific TraD–TraM recognition during F plasmid-mediated bacterial conjugation. Mol. Microbiol. 70, 89–99 (2008).
pubmed: 18717787
doi: 10.1111/j.1365-2958.2008.06391.x
Beranek, A. et al. Thirty-eight C-terminal amino acids of the coupling protein traD of the F-like conjugative resistance plasmid R1 are required and sufficient to confer binding to the substrate selector protein TraM. J. Bacteriol. 186, 6999–7006 (2004).
pubmed: 15466052
pmcid: 522193
doi: 10.1128/JB.186.20.6999-7006.2004
Wong, J. J., Lu, J., Edwards, R. A., Frost, L. S. & Glover, J. M. Structural basis of cooperative DNA recognition by the plasmid conjugation factor, TraM. Nucleic Acids Res. 39, 6775–6788 (2011).
pubmed: 21565799
pmcid: 3159463
doi: 10.1093/nar/gkr296
Rêgo, A. T., Chandran, V. & Waksman, G. Two-step and one-step secretion mechanisms in Gram-negative bacteria: contrasting the type IV secretion system and the chaperone-usher pathway of pilus biogenesis. Biochem. J. 425, 475–488 (2010).
pubmed: 20070257
doi: 10.1042/BJ20091518
Prevost, M. S. & Waksman, G. X-ray crystal structures of the type IVb secretion system DotB ATPases. Protein Sci. 27, 1464–1475 (2018).
pubmed: 29770512
pmcid: 6153414
doi: 10.1002/pro.3439
Jakubowski, S. J., Cascales, E., Krishnamoorthy, V. & Christie, P. J. Agrobacterium tumefaciens VirB9, an outer-membrane-associated component of a type IV secretion system, regulates substrate selection and T-pilus biogenesis. J. Bacteriol. 187, 3486–3495 (2005).
pubmed: 15866936
pmcid: 1112014
doi: 10.1128/JB.187.10.3486-3495.2005
Redzej, A. et al. Structure of a VirD4 coupling protein bound to a VirB type IV secretion machinery. EMBO J. 36, 3080–3095 (2017).
pubmed: 28923826
pmcid: 5916273
doi: 10.15252/embj.201796629
Burns, D. L. Secretion of pertussis toxin from Bordetella pertussis. Toxins 13, 574 (2021).
pubmed: 34437445
pmcid: 8402538
doi: 10.3390/toxins13080574
Dehio, C. & Tsolis, R. M. Type IV effector secretion and subversion of host functions by Bartonella and Brucella species. Curr. Top. Microbiol. Immunol. 413, 269–295 (2017).
pubmed: 29536363
Costa, T. R. D. et al. Structure of the bacterial sex F pilus reveals an assembly of a stoichiometric protein-phospholipid complex. Cell 166, 1436–1444.e10 (2016). The paper presents the structure of the conjugative F pilus, uncovering the incorporation of phospholipid molecules within the molecular architecture of pilus filament, establishing the basis for structural characterization of conjugative pili and leading to a surge in available architectures of other conjugative pili with their respective phospholipid types.
pubmed: 27610568
pmcid: 5018250
doi: 10.1016/j.cell.2016.08.025
Zheng, W. et al. Cryoelectron-microscopic structure of the pKpQIL conjugative pili from carbapenem-resistant Klebsiella pneumoniae. Structure 28, 1321–1328.e2 (2020).
pubmed: 32916103
pmcid: 7710920
doi: 10.1016/j.str.2020.08.010
Kreida, S. et al. Cryo-EM structure of the Agrobacterium tumefaciens T4SS-associated T-pilus reveals stoichiometric protein-phospholipid assembly. Structure 31, 385–394.e4 (2023).
pubmed: 36870333
doi: 10.1016/j.str.2023.02.005
Amro, J. et al. Cryo-EM structure of the Agrobacterium tumefaciens T-pilus reveals the importance of positive charges in the lumen. Structure 31, 375–384 (2023).
pubmed: 36513067
doi: 10.1016/j.str.2022.11.007
Beltran, L. C. et al. Archaeal DNA-import apparatus is homologous to bacterial conjugation machinery. Nat. Commun. 14, 666 (2023).
pubmed: 36750723
pmcid: 9905601
doi: 10.1038/s41467-023-36349-8
Patkowski, J. B. et al. The F-pilus biomechanical adaptability accelerates conjugative dissemination of antimicrobial resistance and biofilm formation. Nat. Commun. 14, 1879 (2023).
pubmed: 37019921
pmcid: 10076315
doi: 10.1038/s41467-023-37600-y
Rozwandowicz, M. et al. Plasmids carrying antimicrobial resistance genes in Enterobacteriaceae. J. Antimicrob. Chemother. 73, 1121–1137 (2018).
pubmed: 29370371
doi: 10.1093/jac/dkx488
Bradley, D. E. Morphological and serological relationships of conjugative pili. Plasmid 4, 155–169 (1980).
pubmed: 6152840
doi: 10.1016/0147-619X(80)90005-0
Paschos, A. et al. An in vivo high-throughput screening approach targeting the type IV secretion system component VirB8 identified inhibitors of Brucella abortus 2308 proliferation. Infect. Immun. 79, 1033–1043 (2011).
pubmed: 21173315
doi: 10.1128/IAI.00993-10
Shaffer, C. L. et al. Peptidomimetic small molecules disrupt type IV secretion system activity in diverse bacterial pathogens. mBio 7, e00221-16 (2016).
pubmed: 27118587
pmcid: 4850256
doi: 10.1128/mBio.00221-16
Ripoll-Rozada, J. et al. Type IV traffic ATPase TrwD as molecular target to inhibit bacterial conjugation. Mol. Microbiol. 100, 912–921 (2016).
pubmed: 26915347
pmcid: 4908816
doi: 10.1111/mmi.13359
Casu, B., Arya, T., Bessette, B. & Baron, C. Fragment-based screening identifies novel targets for inhibitors of conjugative transfer of antimicrobial resistance by plasmid pKM101. Sci. Rep. 7, 14907 (2017).
pubmed: 29097752
pmcid: 5668240
doi: 10.1038/s41598-017-14953-1
Getino, M. & de la Cruz, F. Natural and artificial strategies to control the conjugative transmission of plasmids. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.MTBP-0015-2016 (2018).
Garcia-Cazorla, Y. et al. Conjugation inhibitors compete with palmitic acid for binding to the conjugative traffic ATPase TrwD, providing a mechanism to inhibit bacterial conjugation. J. Biol. Chem. 293, 16923–16930 (2018).
pubmed: 30201608
pmcid: 6204903
doi: 10.1074/jbc.RA118.004716
Arya, T. et al. Fragment-based screening identifies inhibitors of ATPase activity and of hexamer formation of Cagalpha from the Helicobacter pylori type IV secretion system. Sci. Rep. 9, 6474 (2019).
pubmed: 31019200
pmcid: 6482174
doi: 10.1038/s41598-019-42876-6
Alvarez-Rodriguez, I. et al. Type IV coupling proteins as potential targets to control the dissemination of antibiotic resistance. Front. Mol. Biosci. 7, 201 (2020).
pubmed: 32903459
pmcid: 7434980
doi: 10.3389/fmolb.2020.00201
Brown, P. J. B., Chang, J. H. & Fuqua, C. Agrobacterium tumefaciens: a transformative agent for fundamental insights into host-microbe interactions, genome biology, chemical signaling, and cell biology. J. Bacteriol. 205, e0000523 (2023).
pubmed: 36892285
doi: 10.1128/jb.00005-23
Hamilton, T. A. et al. Efficient inter-species conjugative transfer of a CRISPR nuclease for targeted bacterial killing. Nat. Commun. 10, 4544 (2019).
pubmed: 31586051
pmcid: 6778077
doi: 10.1038/s41467-019-12448-3
Vrancianu, C. O., Popa, L. I., Bleotu, C. & Chifiriuc, M. C. Targeting plasmids to limit acquisition and transmission of antimicrobial resistance. Front. Microbiol. 11, 761 (2020).
pubmed: 32435238
pmcid: 7219019
doi: 10.3389/fmicb.2020.00761
Reuter, A. et al. Targeted-antibacterial-plasmids (TAPs) combining conjugation and CRISPR/Cas systems achieve strain-specific antibacterial activity. Nucleic Acids Res. 49, 3584–3598 (2021).
pubmed: 33660775
pmcid: 8034655
doi: 10.1093/nar/gkab126
Bier, E. & Nizet, V. Driving to safety: CRISPR-based genetic approaches to reducing antibiotic resistance. Trends Genet. 37, 745–757 (2021).
pubmed: 33745750
doi: 10.1016/j.tig.2021.02.007
Robledo, M. et al. Targeted bacterial conjugation mediated by synthetic cell-to-cell adhesions. Nucleic Acids Res. 50, 12938–12950 (2022).
pubmed: 36511856
pmcid: 9825185
doi: 10.1093/nar/gkac1164