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A Macrophage Subversion Factor Is Shared by Intracellular and Extracellular Pathogens


Pathogenic bacteria have to resist host immune response and MgtC is used by several intracellular pathogens to promote bacterial multiplication inside macrophages. Here we investigated MgtC’s role in the virulence of an extracellular pathogen, Pseudomonas aeruginosa. A P. aeruginosa mgtC mutant is attenuated in zebrafish embryos, but only in the presence of macrophages. Moreover, this mutant is more rapidly killed by macrophages than the wild-type strain. Both phenotypes can be mimicked upon production of a MgtC antagonistic peptide in wild-type Pseudomonas strain. MgtC thus provides a singular example of a virulence determinant that promotes strategies to subvert the antimicrobial behavior of macrophages, in both intracellular and extracellular pathogens and our results support an intramacrophage stage during in P. aeruginosa acute infection, as well as an interplay between MgtC role and phagosome acidification. In addition, P. aeruginosa MgtC is required for growth in Mg2+ deprived medium, a property shared by MgtC factors from intracellular pathogens, and limits biofilm formation. MgtC may share a similar function in intracellular and extracellular pathogens, with an outcome adapted to the different bacterial lifestyles


Vyšlo v časopise: A Macrophage Subversion Factor Is Shared by Intracellular and Extracellular Pathogens. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004969
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004969

Souhrn

Pathogenic bacteria have to resist host immune response and MgtC is used by several intracellular pathogens to promote bacterial multiplication inside macrophages. Here we investigated MgtC’s role in the virulence of an extracellular pathogen, Pseudomonas aeruginosa. A P. aeruginosa mgtC mutant is attenuated in zebrafish embryos, but only in the presence of macrophages. Moreover, this mutant is more rapidly killed by macrophages than the wild-type strain. Both phenotypes can be mimicked upon production of a MgtC antagonistic peptide in wild-type Pseudomonas strain. MgtC thus provides a singular example of a virulence determinant that promotes strategies to subvert the antimicrobial behavior of macrophages, in both intracellular and extracellular pathogens and our results support an intramacrophage stage during in P. aeruginosa acute infection, as well as an interplay between MgtC role and phagosome acidification. In addition, P. aeruginosa MgtC is required for growth in Mg2+ deprived medium, a property shared by MgtC factors from intracellular pathogens, and limits biofilm formation. MgtC may share a similar function in intracellular and extracellular pathogens, with an outcome adapted to the different bacterial lifestyles


Zdroje

1. Alix E, Blanc-Potard AB MgtC: a key player in intramacrophage survival. Trends Microbiol. 2007; 15: 252–256. 17416526

2. Blanc-Potard AB, Groisman EA The Salmonella selC locus contains a pathogenicity island mediating intramacrophage survival. EMBO J. 1997; 16: 5376–5385. 9311997

3. Lawley TD, Chan K, Thompson LJ, Kim CC, Govoni GR, et al. Genome-wide screen for Salmonella genes required for long-term systemic infection of the mouse. PLoS Pathog. 2006; 2: e11. 16518469

4. Thompson JA, Liu M, Helaine S, Holden DW Contribution of the PhoP/Q regulon to survival and replication of Salmonella enterica serovar Typhimurium in macrophages. Microbiology. 2011; 157: 2084–2093. doi: 10.1099/mic.0.048926-0 21511762

5. Lee EJ, Pontes MH, Groisman EA A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium's own F1Fo ATP synthase. Cell. 2013; 154: 146–156. doi: 10.1016/j.cell.2013.06.004 23827679

6. Garcia Vescovi E, Soncini FC, Groisman EA Mg2+ as an extracellular signal: environmental regulation of Salmonella virulence. Cell. 1996; 84: 165–174. 8548821

7. Lee EJ, Groisman EA Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA. Nature. 2012; 486: 271–275. doi: 10.1038/nature11090 22699622

8. Alix E, Blanc-Potard AB Peptide-assisted degradation of the Salmonella MgtC virulence factor. EMBO J. 2008; 27: 546–557. doi: 10.1038/sj.emboj.7601983 18200043

9. Buchmeier N, Blanc-Potard A, Ehrt S, Piddington D, Riley L, et al. A parallel intraphagosomal survival strategy shared by mycobacterium tuberculosis and Salmonella enterica. Mol Microbiol. 2000; 35: 1375–1382. 10760138

10. Lavigne JP, O'Callaghan D, Blanc-Potard AB Requirement of MgtC for Brucella suis intramacrophage growth: a potential mechanism shared by Salmonella enterica and Mycobacterium tuberculosis for adaptation to a low-Mg2+ environment. Infect Immun. 2005; 73: 3160–3163. 15845525

11. Maloney KE, Valvano MA The mgtC gene of Burkholderia cenocepacia is required for growth under magnesium limitation conditions and intracellular survival in macrophages. Infect Immun. 2006; 74: 5477–5486. 16988222

12. Grabenstein JP, Fukuto HS, Palmer LE, Bliska JB Characterization of phagosome trafficking and identification of PhoP-regulated genes important for survival of Yersinia pestis in macrophages. Infect Immun. 2006; 74: 3727–3741. 16790745

13. Retamal P, Castillo-Ruiz M, Mora GC Characterization of MgtC, a virulence factor of Salmonella enterica Serovar Typhi. PLoS One. 2009; 4: e5551. doi: 10.1371/journal.pone.0005551 19436747

14. Belon C, Gannoun-Zaki L, Lutfalla G, Kremer L, Blanc-Potard AB Mycobacterium marinum MgtC plays a role in phagocytosis but is dispensable for intracellular multiplication. PLoS One. 2014; 9: e116052. doi: 10.1371/journal.pone.0116052 25545682

15. Rang C, Alix E, Felix C, Heitz A, Tasse L, et al. Dual role of the MgtC virulence factor in host and non-host environments. Mol Microbiol. 2007; 63: 605–622. 17176255

16. Blanc-Potard AB, Lafay B MgtC as a horizontally-acquired virulence factor of intracellular bacterial pathogens: evidence from molecular phylogeny and comparative genomics. J Mol Evol. 2003; 57: 479–486. 14708580

17. Ripoll F, Pasek S, Schenowitz C, Dossat C, Barbe V, et al. Non mycobacterial virulence genes in the genome of the emerging pathogen Mycobacterium abscessus. PLoS One. 2009; 4: e5660. doi: 10.1371/journal.pone.0005660 19543527

18. Banin E, Brady KM, Greenberg EP Chelator-induced dispersal and killing of Pseudomonas aeruginosa cells in a biofilm. Appl Environ Microbiol. 2006; 72: 2064–2069. 16517655

19. Mulcahy H, Lewenza S Magnesium limitation is an environmental trigger of the Pseudomonas aeruginosa biofilm lifestyle. PLoS One. 2011; 6: e23307. doi: 10.1371/journal.pone.0023307 21858064

20. Brannon MK, Davis JM, Mathias JR, Hall CJ, Emerson JC, et al. Pseudomonas aeruginosa Type III secretion system interacts with phagocytes to modulate systemic infection of zebrafish embryos. Cell Microbiol. 2009; 11: 755–768. doi: 10.1111/j.1462-5822.2009.01288.x 19207728

21. Garcia-Medina R, Dunne WM, Singh PK, Brody SL Pseudomonas aeruginosa acquires biofilm-like properties within airway epithelial cells. Infect Immun. 2005; 73: 8298–8305. 16299327

22. Sana TG, Hachani A, Bucior I, Soscia C, Garvis S, et al. The second type VI secretion system of Pseudomonas aeruginosa strain PAO1 is regulated by quorum sensing and Fur and modulates internalization in epithelial cells. J Biol Chem. 2012; 287: 27095–27105. doi: 10.1074/jbc.M112.376368 22665491

23. Winsor GL, Lam DK, Fleming L, Lo R, Whiteside MD, et al. Pseudomonas Genome Database: improved comparative analysis and population genomics capability for Pseudomonas genomes. Nucleic Acids Res. 2011; 39: D596–600. doi: 10.1093/nar/gkq869 20929876

24. Roy PH, Tetu SG, Larouche A, Elbourne L, Tremblay S, et al. Complete genome sequence of the multiresistant taxonomic outlier Pseudomonas aeruginosa PA7. PLoS One. 2010; 5: e8842. doi: 10.1371/journal.pone.0008842 20107499

25. Torraca V, Masud S, Spaink HP, Meijer AH Macrophage-pathogen interactions in infectious diseases: new therapeutic insights from the zebrafish host model. Dis Model Mech. 2014; 7: 785–797. doi: 10.1242/dmm.015594 24973749

26. Clatworthy AE, Lee JS, Leibman M, Kostun Z, Davidson AJ, et al. Pseudomonas aeruginosa infection of zebrafish involves both host and pathogen determinants. Infect Immun. 2009; 77: 1293–1303. doi: 10.1128/IAI.01181-08 19168742

27. Lieschke GJ, Oates AC, Crowhurst MO, Ward AC, Layton JE Morphologic and functional characterization of granulocytes and macrophages in embryonic and adult zebrafish. Blood. 2001; 98: 3087–3096. 11698295

28. Clay H, Davis JM, Beery D, Huttenlocher A, Lyons SE, et al. Dichotomous role of the macrophage in early Mycobacterium marinum infection of the zebrafish. Cell Host Microbe. 2007; 2: 29–39. 18005715

29. Bernut A, Herrmann JL, Kissa K, Dubremetz JF, Gaillard JL, et al. Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation. Proc Natl Acad Sci U S A. 2014; 111: E943–952. doi: 10.1073/pnas.1321390111 24567393

30. Engel J, Balachandran P Role of Pseudomonas aeruginosa type III effectors in disease. Curr Opin Microbiol. 2009; 12: 61–66. doi: 10.1016/j.mib.2008.12.007 19168385

31. Bowman EJ, Siebers A, Altendorf K Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc Natl Acad Sci U S A. 1988; 85: 7972–7976. 2973058

32. Friedman L, Kolter R Genes involved in matrix formation in Pseudomonas aeruginosa PA14 biofilms. Mol Microbiol. 2004; 51: 675–690. 14731271

33. Vasseur P, Vallet-Gely I, Soscia C, Genin S, Filloux A The pel genes of the Pseudomonas aeruginosa PAK strain are involved at early and late stages of biofilm formation. Microbiology. 2005; 151: 985–997. 15758243

34. Ma L, Jackson KD, Landry RM, Parsek MR, Wozniak DJ Analysis of Pseudomonas aeruginosa conditional psl variants reveals roles for the psl polysaccharide in adhesion and maintaining biofilm structure postattachment. J Bacteriol. 2006; 188: 8213–8221. 16980452

35. O'Toole GA, Kolter R Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol Microbiol. 1998; 30: 295–304. 9791175

36. Jean-Francois FL, Dai J, Yu L, Myrick A, Rubin E, et al. Binding of MgtR, a Salmonella transmembrane regulatory peptide, to MgtC, a Mycobacterium tuberculosis virulence factor: a structural study. J Mol Biol. 2014; 426: 436–446. doi: 10.1016/j.jmb.2013.10.014 24140750

37. Karimova G, Pidoux J, Ullmann A, Ladant D A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proc Natl Acad Sci U S A. 1998; 95: 5752–5756. 9576956

38. Geiger T, Francois P, Liebeke M, Fraunholz M, Goerke C, et al. The stringent response of Staphylococcus aureus and its impact on survival after phagocytosis through the induction of intracellular PSMs expression. PLoS Pathog. 2012; 8: e1003016. doi: 10.1371/journal.ppat.1003016 23209405

39. Prajsnar TK, Hamilton R, Garcia-Lara J, McVicker G, Williams A, et al. A privileged intraphagocyte niche is responsible for disseminated infection of Staphylococcus aureus in a zebrafish model. Cell Microbiol. 2012; 14: 1600–1619. doi: 10.1111/j.1462-5822.2012.01826.x 22694745

40. Eriksson S, Lucchini S, Thompson A, Rhen M, Hinton JC Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica. Mol Microbiol. 2003; 47: 103–118. 12492857

41. Rathman M, Sjaastad MD, Falkow S Acidification of phagosomes containing Salmonella typhimurium in murine macrophages. Infect Immun. 1996; 64: 2765–2773. 8698506

42. Porte F, Liautard JP, Kohler S Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages. Infect Immun. 1999; 67: 4041–4047. 10417172

43. Skurnik D, Roux D, Aschard H, Cattoir V, Yoder-Himes D, et al. A comprehensive analysis of in vitro and in vivo genetic fitness of Pseudomonas aeruginosa using high-throughput sequencing of transposon libraries. PLoS Pathog. 2013; 9: e1003582. doi: 10.1371/journal.ppat.1003582 24039572

44. Guina T, Wu M, Miller SI, Purvine SO, Yi EC, et al. Proteomic analysis of Pseudomonas aeruginosa grown under magnesium limitation. J Am Soc Mass Spectrom. 2003; 14: 742–751. 12837596

45. Martin-Orozco N, Touret N, Zaharik ML, Park E, Kopelman R, et al. Visualization of vacuolar acidification-induced transcription of genes of pathogens inside macrophages. Mol Biol Cell. 2006; 17: 498–510. 16251362

46. Song B, Leff LG Influence of magnesium ions on biofilm formation by Pseudomonas fluorescens. Microbiol Res. 2006; 161: 355–361. 16517137

47. Robertson EJ, Wolf JM, Casadevall A EDTA inhibits biofilm formation, extracellular vesicular secretion, and shedding of the capsular polysaccharide glucuronoxylomannan by Cryptococcus neoformans. Appl Environ Microbiol. 2012; 78: 7977–7984. doi: 10.1128/AEM.01953-12 22941091

48. Yoon MY, Lee KM, Park Y, Yoon SS Contribution of cell elongation to the biofilm formation of Pseudomonas aeruginosa during anaerobic respiration. PLoS One. 2011; 6: e16105. doi: 10.1371/journal.pone.0016105 21267455

49. Pontes MH, Lee EJ, Choi J, Groisman EA Salmonella promotes virulence by repressing cellulose production. Proc Natl Acad Sci U S A. 2015; 112: 5183–5188. doi: 10.1073/pnas.1500989112 25848006

50. Yang Y, Labesse G, Carrere-Kremer S, Esteves K, Kremer L, et al. (2012) The C-terminal domain of the virulence factor MgtC is a divergent ACT domain. J Bacteriol 194: 6255–6263. doi: 10.1128/JB.01424-12 22984256

51. Hoang TT, Kutchma AJ, Becher A, Schweizer HP Integration-proficient plasmids for Pseudomonas aeruginosa: site-specific integration and use for engineering of reporter and expression strains. Plasmid. 2000; 43: 59–72. 10610820

52. Lamason RL, Mohideen MA, Mest JR, Wong AC, Norton HL, et al. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science. 2005; 310: 1782–1786. 16357253

53. Soscia C, Hachani A, Bernadac A, Filloux A, Bleves S Cross talk between type III secretion and flagellar assembly systems in Pseudomonas aeruginosa. J Bacteriol. 2007; 189: 3124–3132. 17307856

54. Del Porto P, Cifani N, Guarnieri S, Di Domenico EG, Mariggio MA, et al. Dysfunctional CFTR alters the bactericidal activity of human macrophages against Pseudomonas aeruginosa. PLoS One. 2011; 6: e19970. doi: 10.1371/journal.pone.0019970 21625641

55. Gannoun-Zaki L, Belon C, Dupont C, Hilbert F, Kremer L, et al. Overexpression of the Salmonella KdpF membrane peptide modulates expression of kdp genes and intramacrophage growth. FEMS Microbiol Lett. 2014; 359: 34–41. doi: 10.1111/1574-6968.12559 25197761

56. Vallet I, Olson JW, Lory S, Lazdunski A, Filloux A The chaperone/usher pathways of Pseudomonas aeruginosa: identification of fimbrial gene clusters (cup) and their involvement in biofilm formation. Proc Natl Acad Sci U S A. 2001; 98: 6911–6916. 11381121

57. Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, et al. Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 2008; 36: W465–469. doi: 10.1093/nar/gkn180 18424797

58. Gastebois A, Blanc Potard AB, Gribaldo S, Beau R, Latge JP, et al. Phylogenetic and functional analysis of Aspergillus fumigatus MGTC, a fungal protein homologous to a bacterial virulence factor. Appl Environ Microbiol. 2011; 77: 4700–4703. doi: 10.1128/AEM.00243-11 21602378

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