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Abstract

The type VIIb protein secretion system (T7SSb) is found in (firmicute) bacteria and has been shown to mediate interbacterial competition. EssC is a membrane-bound ATPase that is a critical component of the T7SSb and plays a key role in substrate recognition. Prior analysis of available genome sequences of the foodborne bacterial pathogen has shown that although the T7SSb was encoded as part of the core genome, EssC could be found as one of seven different sequence variants. While each sequence variant was associated with a specific suite of candidate substrate proteins encoded immediately downstream of , many LXG-domain proteins were encoded across multiple sequence variants. Here, we have extended this analysis using a diverse collection of 37 930 . genomes. We have identified a rare eighth variant of EssC present in ten lineage III genomes. These genomes also encode a large toxin of the rearrangement hotspot (Rhs) repeat family adjacent to , along with a probable immunity protein and three small accessory proteins. We have further identified nine novel LXG-domain proteins, and four additional chromosomal hotspots across genomes where LXG proteins can be encoded. The eight EssC variants were also found in other species, with additional novel EssC types also identified. Across the genus, species frequently encoded multiple EssC types, indicating that T7SSb diversity is a primary feature of the genus .

Funding
This study was supported by the:
  • Biotechnology and Biological Sciences Research Council (Award BB/M011186/1)
    • Principle Award Recipient: StephenR Garrett
  • Wellcome Trust (Award 224151/Z/21/Z)
    • Principle Award Recipient: TracyPalmer
  • Wellcome Trust (Award 10183/Z/15/Z)
    • Principle Award Recipient: TracyPalmer
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-06-06
2024-03-29
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References

  1. Bauer MA, Kainz K, Carmona-Gutierrez D, Madeo F. Microbial wars: competition in ecological niches and within the microbiome. Microb Cell 2018; 5:215–219 [View Article] [PubMed]
    [Google Scholar]
  2. Coyte KZ, Rakoff-Nahoum S. Understanding competition and cooperation within the mammalian gut microbiome. Curr Biol 2019; 29:R538–R544 [View Article] [PubMed]
    [Google Scholar]
  3. Filloux A. Bacterial protein secretion systems: game of types. Microbiology 2022; 168:001193 [View Article] [PubMed]
    [Google Scholar]
  4. Bowman L, Palmer T. The type VII secretion system of Staphylococcus. Annu Rev Microbiol 2021; 75:471–494
    [Google Scholar]
  5. Klein TA, Ahmad S, Whitney JC. Contact-dependent interbacterial antagonism mediated by protein secretion machines. Trends Microbiol 2020; 28:387–400 [View Article] [PubMed]
    [Google Scholar]
  6. Abdallah AM, Gey van Pittius NC, Champion PAD, Cox J, Luirink J et al. Type VII secretion – mycobacteria show the way. Nat Rev Microbiol 2007; 5:883–891 [View Article] [PubMed]
    [Google Scholar]
  7. Bunduc CM, Fahrenkamp D, Wald J, Ummels R, Bitter W et al. Structure and dynamics of a mycobacterial type VII secretion system. Nature 2021; 593:445–448 [View Article] [PubMed]
    [Google Scholar]
  8. Beckham KSH, Ciccarelli L, Bunduc CM, Mertens HDT, Ummels R et al. Structure of the mycobacterial ESX-5 type VII secretion system membrane complex by single-particle analysis. Nat Microbiol 2017; 2:17047 [View Article] [PubMed]
    [Google Scholar]
  9. Beckham KSH, Ritter C, Chojnowski G, Ziemianowicz DS, Mullapudi E et al. Structure of the mycobacterial ESX-5 type VII secretion system pore complex. Sci Adv 2021; 7:eabg9923 [View Article] [PubMed]
    [Google Scholar]
  10. Zoltner M, Ng WMAV, Money JJ, Fyfe PK, Kneuper H et al. EssC: domain structures inform on the elusive translocation channel in the type VII secretion system. Biochem J 2016; 473:1941–1952 [View Article] [PubMed]
    [Google Scholar]
  11. Bobrovskyy M, Oh SY, Missiakas D. Contribution of the EssC ATPase to the assembly of the type 7b secretion system in Staphylococcus aureus. J Biol Chem 2022; 298:102318 [View Article] [PubMed]
    [Google Scholar]
  12. Sysoeva TA, Zepeda-Rivera MA, Huppert LA, Burton BM. Dimer recognition and secretion by the ESX secretion system in Bacillus subtilis. Proc Natl Acad Sci 2014; 111:7653–7658 [View Article] [PubMed]
    [Google Scholar]
  13. Renshaw PS, Lightbody KL, Veverka V, Muskett FW, Kelly G et al. Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6. EMBO J 2005; 24:2491–2498 [View Article] [PubMed]
    [Google Scholar]
  14. Abdallah AM, Verboom T, Hannes F, Safi M, Strong M et al. A specific secretion system mediates PPE41 transport in pathogenic mycobacteria. Mol Microbiol 2006; 62:667–679 [View Article] [PubMed]
    [Google Scholar]
  15. McLaughlin B, Chon JS, MacGurn JA, Carlsson F, Cheng TL et al. A mycobacterium ESX-1-secreted virulence factor with unique requirements for export. PLoS Pathog 2007; 3:e105 [View Article] [PubMed]
    [Google Scholar]
  16. Whitney JC, Peterson SB, Kim J, Pazos M, Verster AJ et al. A broadly distributed toxin family mediates contact-dependent antagonism between gram-positive bacteria. Elife 2017; 6:e26938 [View Article] [PubMed]
    [Google Scholar]
  17. Cao Z, Casabona MG, Kneuper H, Chalmers JD, Palmer T. The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria. Nat Microbiol 2016; 2:16183 [View Article] [PubMed]
    [Google Scholar]
  18. Ulhuq FR, Gomes MC, Duggan GM, Guo M, Mendonca C et al. A membrane-depolarizing toxin substrate of the Staphylococcus aureus type VII secretion system mediates intraspecies competition. Proc Natl Acad Sci 2020; 117:20836–20847 [View Article] [PubMed]
    [Google Scholar]
  19. Klein TA, Grebenc DW, Shah PY, McArthur OD, Dickson BH et al. Dual targeting factors are required for LXG toxin export by the bacterial type VIIb secretion system. mBio 2022; 13:e0213722 [View Article] [PubMed]
    [Google Scholar]
  20. Chatterjee A, Willett JLE, Dunny GM, Duerkop BA. Phage infection and sub-lethal antibiotic exposure mediate Enterococcus faecalis type VII secretion system dependent inhibition of bystander bacteria. PLoS Genet 2021; 17:e1009204 [View Article] [PubMed]
    [Google Scholar]
  21. Kobayashi K. Diverse LXG toxin and antitoxin systems specifically mediate intraspecies competition in Bacillus subtilis biofilms. PLoS Genet 2021; 17:e1009682 [View Article] [PubMed]
    [Google Scholar]
  22. Bowran K, Palmer T. Extreme genetic diversity in the type VII secretion system of Listeria monocytogenes suggests a role in bacterial antagonism. Microbiology 2021; 167:001034 [View Article] [PubMed]
    [Google Scholar]
  23. Lourenco A, Linke K, Wagner M, Stessl B. The saprophytic lifestyle of Listeria monocytogenes and entry into the food-processing environment. Front Microbiol 2022; 13:789801 [View Article] [PubMed]
    [Google Scholar]
  24. Ziegler M, Kent D, Stephan R, Guldimann C. Growth potential of Listeria monocytogenes in twelve different types of RTE salads: impact of food matrix, storage temperature and storage time. Int J Food Microbiol 2019; 296:83–92 [View Article] [PubMed]
    [Google Scholar]
  25. Pizarro-Cerdá J, Cossart P. Microbe profile: Listeria monocytogenes: a paradigm among intracellular bacterial pathogens. Microbiology 2019; 165:719–721 [View Article] [PubMed]
    [Google Scholar]
  26. Radoshevich L, Cossart P. Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis. Nat Rev Microbiol 2018; 16:32–46 [View Article] [PubMed]
    [Google Scholar]
  27. Disson O, Moura A, Lecuit M. Making sense of the biodiversity and virulence of Listeria monocytogenes. Trends Microbiol 2021; 29:811–822 [View Article] [PubMed]
    [Google Scholar]
  28. Moura A, Criscuolo A, Pouseele H, Maury MM, Leclercq A et al. Whole genome-based population biology and epidemiological surveillance of Listeria monocytogenes. Nat Microbiol 2016; 2:16185 [View Article] [PubMed]
    [Google Scholar]
  29. Rychli K, Wagner EM, Ciolacu L, Zaiser A, Tasara T et al. Comparative genomics of human and non-human Listeria monocytogenes sequence type 121 strains. PLoS One 2017; 12:e0176857 [View Article] [PubMed]
    [Google Scholar]
  30. Gurevich A, Saveliev V, Vyahhi N, Tesler G. QUAST: quality assessment tool for genome assemblies. Bioinformatics 2013; 29:1072–1075 [View Article] [PubMed]
    [Google Scholar]
  31. Ragon M, Wirth T, Hollandt F, Lavenir R, Lecuit M et al. A new perspective on Listeria monocytogenes evolution. PLoS Pathog 2008; 4:e1000146 [View Article] [PubMed]
    [Google Scholar]
  32. Silva M, Machado MP, Silva DN, Rossi M, Moran-Gilad J et al. chewBBACA: a complete suite for gene-by-gene schema creation and strain identification. Microb Genom 2018; 4:e000166 [View Article] [PubMed]
    [Google Scholar]
  33. Moura A, Tourdjman M, Leclercq A, Hamelin E, Laurent E et al. Real-time whole-genome sequencing for surveillance of Listeria monocytogenes, France. Emerg Infect Dis 2017; 23:1462–1470 [View Article] [PubMed]
    [Google Scholar]
  34. Zhou Z, Alikhan N-F, Sergeant MJ, Luhmann N, Vaz C et al. GrapeTree: visualization of core genomic relationships among 100,000 bacterial pathogens. Genome Res 2018; 28:1395–1404 [View Article]
    [Google Scholar]
  35. Hyatt D, Chen GL, Locascio PF, Land ML, Larimer FW et al. Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics 2010; 11:119 [View Article] [PubMed]
    [Google Scholar]
  36. Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J et al. BLAST+: architecture and applications. BMC Bioinformatics 2009; 10:421 [View Article] [PubMed]
    [Google Scholar]
  37. Cuccuru G, Orsini M, Pinna A, Sbardellati A, Soranzo N et al. Orione, a web-based framework for NGS analysis in microbiology. Bioinformatics 2014; 30:1928–1929 [View Article] [PubMed]
    [Google Scholar]
  38. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article]
    [Google Scholar]
  39. Arndt D, Grant JR, Marcu A, Sajed T, Pon A et al. PHASTER: a better, faster version of the PHAST phage search tool. Nucleic Acids Res 2016; 44:W16–W21 [View Article]
    [Google Scholar]
  40. Zhou Y, Liang Y, Lynch KH, Dennis JJ, Wishart DS. PHAST: a fast phage search tool. Nucleic Acids Res 2011; 39:W347–W352 [View Article]
    [Google Scholar]
  41. Darling ACE, Mau B, Blattner FR, Perna NT. Mauve: multiple alignment of conserved genomic sequence with rearrangements. Genome Res 2004; 14:1394–1403 [View Article] [PubMed]
    [Google Scholar]
  42. Edgar RC. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 2004; 5:113 [View Article] [PubMed]
    [Google Scholar]
  43. Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 2004; 32:1792–1797 [View Article] [PubMed]
    [Google Scholar]
  44. Almagro Armenteros JJ, Tsirigos KD, Sønderby CK, Petersen TN, Winther O et al. SignalP 5.0 improves signal peptide predictions using deep neural networks. Nat Biotechnol 2019; 37:420–423 [View Article] [PubMed]
    [Google Scholar]
  45. Hallgren J, Tsirigos KD, Pedersen MD, Almagro Armenteros JJ, Marcatili P et al. DeepTMHMM predicts alpha and beta transmembrane proteins using deep neural networks. bioRxiv [View Article]
    [Google Scholar]
  46. Jumper J, Evans R, Pritzel A, Green T, Figurnov M et al. Highly accurate protein structure prediction with AlphaFold. Nature 2021; 596:583–589 [View Article] [PubMed]
    [Google Scholar]
  47. Holm L. Dali server: structural unification of protein families. Nucleic Acids Res 2022; 50:W210–W215 [View Article]
    [Google Scholar]
  48. Kumar S, Stecher G, Tamura K. MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for bigger datasets. Mol Biol Evol 2016; 33:1870–1874 [View Article]
    [Google Scholar]
  49. Saha CK, Sanches Pires R, Brolin H, Delannoy M, Atkinson GC. FlaGs and webFlaGs: discovering novel biology through the analysis of gene neighbourhood conservation. Bioinformatics 2021; 37:1312–1314 [View Article] [PubMed]
    [Google Scholar]
  50. Gilchrist CLM, Chooi YH. clinker & clustermap.js: automatic generation of gene cluster comparison figures. Bioinformatics 2021; 37:2473–2475 [View Article] [PubMed]
    [Google Scholar]
  51. Kneuper H, Cao ZP, Twomey KB, Zoltner M, Jäger F et al. Heterogeneity in ess transcriptional organization and variable contribution of the Ess/type VII protein secretion system to virulence across closely related Staphylocccus aureus strains. Mol Microbiol 2014; 93:928–943 [View Article] [PubMed]
    [Google Scholar]
  52. Alcoforado Diniz J, Coulthurst SJ. Intraspecies competition in Serratia marcescens is mediated by type VI-secreted Rhs effectors and a conserved effector-associated accessory protein. J Bacteriol 2015; 197:2350–2360 [View Article] [PubMed]
    [Google Scholar]
  53. Koskiniemi S, Lamoureux JG, Nikolakakis KC, t’Kint de Roodenbeke C, Kaplan MD et al. Rhs proteins from diverse bacteria mediate intercellular competition. Proc Natl Acad Sci 2013; 110:7032–7037 [View Article] [PubMed]
    [Google Scholar]
  54. Busby JN, Panjikar S, Landsberg MJ, Hurst MRH, Lott JS. The BC component of ABC toxins is an RHS-repeat-containing protein encapsulation device. Nature 2013; 501:547–550 [View Article] [PubMed]
    [Google Scholar]
  55. Günther P, Quentin D, Ahmad S, Sachar K, Gatsogiannis C et al. Structure of a bacterial Rhs effector exported by the type VI secretion system. PLoS Pathog 2022; 18:e1010182 [View Article] [PubMed]
    [Google Scholar]
  56. Tang JY, Bullen NP, Ahmad S, Whitney JC. Diverse NADase effector families mediate interbacterial antagonism via the type VI secretion system. J Biol Chem 2018; 293:1504–1514 [View Article] [PubMed]
    [Google Scholar]
  57. Jackson AP, Thomas GH, Parkhill J, Thomson NR. Evolutionary diversification of an ancient gene family (rhs) through C-terminal displacement. BMC Genomics 2009; 10:584 [View Article] [PubMed]
    [Google Scholar]
  58. Warne B, Harkins CP, Harris SR, Vatsiou A, Stanley-Wall N et al. The Ess/type VII secretion system of Staphylococcus aureus shows unexpected genetic diversity. BMC Genomics 2016; 17:222 [View Article]
    [Google Scholar]
  59. Spencer BL, Job AM, Robertson CM, Hameed ZA, Serchejian C et al. Heterogeneity of the group B streptococcal type VII secretion system and influence on colonization of the female genital tract. bioRxiv [View Article]
    [Google Scholar]
  60. Jamet A, Nassif X. New players in the toxin field: polymorphic toxin systems in bacteria. mBio 2015; 6:e00285-15 [View Article] [PubMed]
    [Google Scholar]
  61. Zhang D, de Souza RF, Anantharaman V, Iyer LM, Aravind L. Polymorphic toxin systems: comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics. Biol Direct 2012; 7:18 [View Article] [PubMed]
    [Google Scholar]
  62. Shukla A, Pallen M, Anthony M, White SA. The homodimeric GBS1074 from Streptococcus agalactiae. Acta Crystallogr Sect F Struct Biol Cryst Commun 2010; 66:1421–1425 [View Article] [PubMed]
    [Google Scholar]
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