Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence


Autoři: Vincenzo Torraca aff001;  Myrsini Kaforou aff003;  Jayne Watson aff004;  Gina M. Duggan aff001;  Hazel Guerrero-Gutierrez aff001;  Sina Krokowski aff001;  Michael Hollinshead aff005;  Thomas B. Clarke aff001;  Rafal J. Mostowy aff006;  Gillian S. Tomlinson aff008;  Vanessa Sancho-Shimizu aff003;  Abigail Clements aff004;  Serge Mostowy aff001
Působiště autorů: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom aff001;  Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, United Kingdom aff002;  Department of Paediatrics, Division of Medicine, Imperial College London, London, United Kingdom aff003;  Faculty of Natural Sciences, Department of Life Sciences, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom aff004;  Division of Virology, Department of Pathology, Cambridge University, Cambridge, United Kingdom aff005;  Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland aff006;  Faculty of Medicine, School of Public Health, Imperial College London, London, United Kingdom aff007;  Division of Infection and Immunity, University College London, London, United Kingdom aff008;  Department of Virology, Division of Medicine, Imperial College London, London, United Kingdom aff009
Vyšlo v časopise: Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008006
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008006

Souhrn

Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model of Shigella infection, we discover that S. sonnei is more virulent than S. flexneri in vivo. Whole animal dual-RNAseq and testing of bacterial mutants suggest that S. sonnei virulence depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show in vivo using zebrafish and ex vivo using human neutrophils that S. sonnei O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables S. sonnei to resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of S. sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal dose of S. sonnei are protected against a secondary lethal dose of S. sonnei in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against S. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasing S. sonnei burden in developing countries.

Klíčová slova:

Larvae – Macrophages – Neutrophils – Shigella – Shigella flexneri – Shigellosis – Test statistics – Zebrafish


Zdroje

1. Khalil IA, Troeger C, Blacker BF, Rao PC, Brown A, Atherly DE, et al. Morbidity and mortality due to Shigella and enterotoxigenic Escherichia coli diarrhoea: the global burden of disease study 1990–2016. Lancet Infect Dis. 2018;18: 1229–1240. doi: 10.1016/S1473-3099(18)30475-4 30266330

2. Kotloff KL, Riddle MS, Platts-Mills JA, Pavlinac P, Zaidi AKM. Shigellosis. Lancet. 2018;391: 801–812. doi: 10.1016/S0140-6736(17)33296-8 29254859

3. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): A prospective, case-control study. Lancet. 2013;382: 209–222. doi: 10.1016/S0140-6736(13)60844-2 23680352

4. World Health Organization. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. WHO Press. WHO Press; 2017.

5. Baker KS, Dallman TJ, Field N, Childs T, Mitchell H, Day M, et al. Horizontal antimicrobial resistance transfer drives epidemics of multiple Shigella species. Nat Commun. 2018;9: 1462. doi: 10.1038/s41467-018-03949-8 29654279

6. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303: 1532–1435. doi: 10.1126/science.1092385 15001782

7. Girardin SE, Boneca IG, Carneiro LAM, Antignac A, Jéhanno M, Viala J, et al. Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan. Science. 2003;300: 1584–1587. doi: 10.1126/science.1084677 12791997

8. Ogawa M, Yoshimori T, Suzuki T, Sagara H, Mizushima N, Sasakawa C. Escape of intracellular Shigella from autophagy. Science. 2005;307: 727–731. doi: 10.1126/science.1106036 15576571

9. Li P, Jiang W, Yu Q, Liu W, Zhou P, Li J, et al. Ubiquitination and degradation of GBPs by a Shigella effector to suppress host defence. Nature. 2017;551: 378–383. doi: 10.1038/nature24467 29144452

10. Wandel MP, Pathe C, Werner EI, Ellison CJ, Boyle KB, von der Malsburg A, et al. GBPs inhibit motility of Shigella flexneri but are targeted for degradation by the bacterial ubiquitin ligase IpaH9.8. Cell Host Microbe. 2017;22: 507–518.e5. doi: 10.1016/j.chom.2017.09.007 29024643

11. Krokowski S, Lobato-Márquez D, Chastanet A, Pereira PM, Angelis D, Galea D, et al. Septins recognize and entrap dividing bacterial cells for delivery to lysosomes. Cell Host Microbe. 2018;24: 866–874.e4. doi: 10.1016/j.chom.2018.11.005 30543779

12. Mostowy S, Bonazzi M, Hamon MA, Tham TN, Mallet A, Lelek M, et al. Entrapment of intracytosolic bacteria by septin cage-like structures. Cell Host Microbe. 2010;8: 433–444. doi: 10.1016/j.chom.2010.10.009 21075354

13. Pupo GM, Lan R, Reeves PR. Multiple independent origins of Shigella clones of Escherichia coli and convergent evolution of many of their characteristics. Proc Natl Acad Sci. 2000;97: 10567–10572. doi: 10.1073/pnas.180094797 10954745

14. Holt KE, Baker S, Weill F-X, Holmes EC, Kitchen A, Yu J, et al. Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe. Nat Genet. 2012;44: 1056–1059. doi: 10.1038/ng.2369 22863732

15. Kotloff KL, Winickoff JP, Ivanoff B, Clemens JD, Swerdlow DL, Sansonetti PJ, et al. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull World Health Organ. 1999;77: 651–666. 10516787

16. Thompson CN, Duy PT, Baker S. The rising dominance of Shigella sonnei: an intercontinental shift in the etiology of bacillary dysentery. PLoS Negl Trop Dis. 2015;9: e0003708. doi: 10.1371/journal.pntd.0003708 26068698

17. Sack DA, Hoque AT, Huq A, Etheridge M. Is protection against shigellosis induced by natural infection with Plesiomonas shigelloides? Lancet. 1994;343: 1413–1415. doi: 10.1016/s0140-6736(94)92531-3 7910890

18. Anderson MC, Vonaesch P, Saffarian A, Marteyn BS, Sansonetti PJ. Shigella sonnei encodes a functional T6SS used for interbacterial competition and niche occupancy. Cell Host Microbe. 2017;21: 769–776.e3. doi: 10.1016/j.chom.2017.05.004 28618272

19. Torraca V, Mostowy S. Zebrafish infection: from pathogenesis to cell biology. Trends Cell Biol. 2018;28: 143–156. doi: 10.1016/j.tcb.2017.10.002 29173800

20. Gomes MC, Mostowy S. The case for modeling human infection in zebrafish. Trends Microbiol. 2019; doi: 10.1016/j.tim.2019.08.005 31604611

21. Duggan GM, Mostowy S. Use of zebrafish to study Shigella infection. Dis Model Mech. 2018;11: dmm032151. doi: 10.1242/dmm.032151 29590642

22. Mostowy S, Boucontet L, Mazon Moya MJ, Sirianni A, Boudinot P, Hollinshead M, et al. The zebrafish as a new model for the in vivo study of Shigella flexneri interaction with phagocytes and bacterial autophagy. PLoS Pathog. 2013;9: e1003588. doi: 10.1371/journal.ppat.1003588 24039575

23. Willis AR, Moore C, Mazon-Moya M, Krokowski S, Lambert C, Till R, et al. Injections of predatory bacteria work alongside host immune cells to treat Shigella infection in zebrafish larvae. Curr Biol. 2016;26: 3343–3351. doi: 10.1016/j.cub.2016.09.067 27889262

24. Mazon-Moya MJ, Willis AR, Torraca V, Boucontet L, Shenoy AR, Colucci-Guyon E, et al. Septins restrict inflammation and protect zebrafish larvae from Shigella infection. PLoS Pathog. 2017;13: e1006467. doi: 10.1371/journal.ppat.1006467 28650995

25. Willis AR, Torraca V, Gomes MC, Shelley J, Mazon-Moya M, Filloux A, et al. Shigella-induced emergency granulopoiesis protects zebrafish larvae from secondary infection. MBio. 2018;9. doi: 10.1128/mBio.00933-18 29946048

26. Caboni M, Pédron T, Rossi O, Goulding D, Pickard D, Citiulo F, et al. An O-antigen capsule modulates bacterial pathogenesis in Shigella sonnei. PLoS Pathog. 2015;11: e1004749. doi: 10.1371/journal.ppat.1004749 25794007

27. McVicker G, Tang CM. Deletion of toxin–antitoxin systems in the evolution of Shigella sonnei as a host-adapted pathogen. Nat Microbiol. 2017;2: 16204. doi: 10.1038/nmicrobiol.2016.204 27819667

28. Liu B, Knirel YA, Feng L, Perepelov A V., Senchenkova SN, Wang Q, et al. Structure and genetics of Shigella O-antigens. FEMS Microbiol Rev. 2008;32: 627–653. doi: 10.1111/j.1574-6976.2008.00114.x 18422615

29. François M, Le Cabec V, Dupont MA, Sansonetti PJ, Maridonneau-Parini I. Induction of necrosis in human neutrophils by Shigella flexneri requires type III secretion, IpaB and IpaC invasins, and actin polymerization. Infect Immun. 2000;68: 1289–1296. doi: 10.1128/iai.68.3.1289-1296.2000 10678940

30. Wang L, Wang Q, Reeves PR. The variation of O-antigens in Gram-negative bacteria. Subcell Biochem. 2010;53: 123–152. doi: 10.1007/978-90-481-9078-2_6 20593265

31. Shepherd JG, Wang L, Reeves PR. Comparison of O-antigen gene clusters of Escherichia coli (Shigella) sonnei and Plesiomonas shigelloides O17: sonnei gained its current plasmid-borne O-antigen genes from P. shigelloides in a recent event. Infect Immun. 2000;68: 6056–6061. doi: 10.1128/iai.68.10.6056-6061.2000 10992522

32. Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY, Oosting M, et al. BCG vaccination protects against experimental viral Infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe. 2018;23: 89–100.e5. doi: 10.1016/j.chom.2017.12.010 29324233

33. Netea MG, Joosten LAB, Latz E, Mills KHG, Natoli G, Stunnenberg HG, et al. Trained immunity: a program of innate immune memory in health and disease. Science. 2016;352: aaf1098–aaf1098. doi: 10.1126/science.aaf1098 27102489

34. Ashkenazi S, May-Zahav M, Dinari G, Gabbay U, Zilberberg R, Samra Z. Recent trends in the epidemiology of Shigella species in Israel. Clin Infect Dis. 1993;17: 897–899. doi: 10.1093/clinids/17.5.897 8286636

35. Ashkenazi S. Shigella infections in children: New insights. Semin Pediatr Infect Dis. 2004;15: 246–252. doi: 10.1053/j.spid.2004.07.005 15494948

36. Ranjbar R, Soltan Dallal MM, Talebi M, Pourshafie MR. Increased isolation and characterization of Shigella sonnei obtained from hospitalized children in Tehran, Iran. J Health Popul Nutr. 2008;26: 426–430. doi: 10.3329/jhpn.v26i4.1884 19069621

37. Simon AK, Hollander GA, McMichael A. Evolution of the immune system in humans from infancy to old age. Proc R Soc B Biol Sci. 2015;282: 20143085. doi: 10.1098/rspb.2014.3085 26702035

38. Zhao L, Xiong Y, Meng D, Guo J, Li Y, Liang L, et al. An 11-year study of shigellosis and Shigella species in Taiyuan, China: active surveillance, epidemic characteristics, and molecular serotyping. J Infect Public Health. 2017;10: 794–798. doi: 10.1016/j.jiph.2017.01.009 28188118

39. Arts RJW, Joosten LAB, Netea MG. The potential role of trained immunity in autoimmune and autoinflammatory disorders. Front Immunol. 2018;9: 298. doi: 10.3389/fimmu.2018.00298 29515591

40. Butkeviciute E, Jones CE, Smith SG. Heterologous effects of infant BCG vaccination: potential mechanisms of immunity. Future Microbiol. 2018;13: 1193–1208. doi: 10.2217/fmb-2018-0026 30117744

41. Novakovic B, Messina NL, Curtis N. The heterologous effects of bacillus Calmette-Guérin (BCG) vaccine and trained innate immunity. The Value of BCG and TNF in Autoimmunity. 2018. pp. 71–90. doi: 10.1016/B978-0-12-814603-3.00006–9

42. Datsenko KA, Wanner BL. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci. 2000;97: 6640–6645. doi: 10.1073/pnas.120163297 10829079

43. Watson JL, Sanchez-Garrido J, Goddard PJ, Torraca V, Mostowy S, Shenoy AR, et al. Shigella sonnei O-antigen inhibits internalisation, vacuole escape and inflammasome activation. bioRxiv. Cold Spring Harbor Laboratory; 2019; 799379. doi: 10.1101/799379

44. Standish AJ, Weiser JN. Human neutrophils kill Streptococcus pneumoniae via serine proteases. J Immunol. 2009;183: 2602–2609. doi: 10.4049/jimmunol.0900688 19620298

45. Tapper H, Sundler R. Bafilomycin A1 inhibits lysosomal, phagosomal, and plasma membrane H(+)-ATPase and induces lysosomal enzyme secretion in macrophages. J Cell Physiol. John Wiley & Sons, Ltd; 1995;163: 137–144. doi: 10.1002/jcp.1041630116 7896890

46. Prince LR, Bianchi SM, Vaughan KM, Bewley MA, Marriott HM, Walmsley SR, et al. Subversion of a lysosomal pathway regulating neutrophil apoptosis by a major bacterial toxin, pyocyanin. J Immunol. 2008;180: 3502–11. doi: 10.4049/jimmunol.180.5.3502 18292577

47. Curado S, Stainier DYR, Anderson RM. Nitroreductase-mediated cell/tissue ablation in zebrafish: a spatially and temporally controlled ablation method with applications in developmental and regeneration studies. Nat Protoc. 2008;3: 948–954. doi: 10.1038/nprot.2008.58 18536643

48. Roca FJ, Ramakrishnan L. TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species. Cell. 2013;153: 521–534. doi: 10.1016/j.cell.2013.03.022 23582643

49. Tyrkalska SD, Candel S, Angosto D, Gómez-Abellán V, Martín-Sánchez F, García-Moreno D, et al. Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins. Nat Commun. 2016;7: 12077. doi: 10.1038/ncomms12077 27363812

50. Levitte S, Adams KN, Berg RD, Cosma CL, Urdahl KB, Ramakrishnan L. Mycobacterial acid tolerance enables phagolysosomal survival and establishment of tuberculous infection in vivo. Cell Host Microbe. 2016;20: 250–258. doi: 10.1016/j.chom.2016.07.007 27512905

51. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15: 550. doi: 10.1186/s13059-014-0550-8 25516281

52. R Development Core Team. R: A language and environment for statistical computing. 2011.

53. Ge SX, Jung D. ShinyGO: a graphical enrichment tool for animals and plants. bioRxiv. 2018; doi: 10.1101/315150

54. Huerta-Cepas J, Forslund K, Coelho LP, Szklarczyk D, Jensen LJ, Von Mering C, et al. Fast genome-wide functional annotation through orthology assignment by eggNOG-mapper. Mol Biol Evol. Oxford University Press; 2017;34: 2115–2122. doi: 10.1093/molbev/msx148 28460117

55. Sergushichev AA. An algorithm for fast preranked gene set enrichment analysis using cumulative statistic calculation. bioRxiv. Cold Spring Harbor Laboratory; 2016; 060012. doi: 10.1101/060012

56. Anderson M, Sansonetti PJ, Marteyn BS. Shigella diversity and changing landscape: insights for the twenty-first century. Front Cell Infect Microbiol. 2016;6: 45. doi: 10.3389/fcimb.2016.00045 27148494

Štítky
Hygiena a epidemiologie Infekční lékařství Laboratoř

Článek vyšel v časopise

PLOS Pathogens


2019 Číslo 12

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Nová éra v léčbě migrény
nový kurz
Autoři: MUDr. Eva Medová, MUDr. Tomáš Nežádal, Ph.D.

Význam nutraceutik u kardiovaskulárních onemocnění
Autoři:

Pneumowebinář
Autoři:

White paper - jak vidíme optimální péči o zubní náhrady
Autoři: MUDr. Jindřich Charvát, CSc.

Faktory ovlivňující léčbu levotyroxinem

Všechny kurzy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se