The νSaα Specific Lipoprotein Like Cluster () of . USA300 Contributes to Immune Stimulation and Invasion in Human Cells
Highly pathogenic and epidemic Staphylococcus aureus strains carry a pathogenicity island in their genome that contains a cluster of lipoprotein-encoding genes termed lpl. As the role lpl in virulence is still unclear, we deleted the entire lpl cluster in the community-acquired methicillin-resistant S. aureus (CA-MRSA) USA300 and found that the mutant was defective in stimulation of pro-inflammatory cytokines in human immune cells. Moreover, the major finding highlighted in this study is that the lpl cluster contributes to invasion into non-professional phagocytes such as epithelial cells and keratinocytes. Furthermore, the lpl-dependent increase in invasive activity, most likely, accounts for the enhanced bacterial burden observed in a murine kidney abscess model. In general, internalization of a pathogen into host epithelial cells shields the pathogen from immune defense and antibiotic treatment. However, further investigation is needed to clarify whether the increased ability to invade host cells is responsible for the potent disseminative activity and hypervirulent phenotype characterizing the νSaα type I island expressing S. aureus strains, including the USA300 CA-MRSA strain.
Vyšlo v časopise:
The νSaα Specific Lipoprotein Like Cluster () of . USA300 Contributes to Immune Stimulation and Invasion in Human Cells. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004984
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004984
Souhrn
Highly pathogenic and epidemic Staphylococcus aureus strains carry a pathogenicity island in their genome that contains a cluster of lipoprotein-encoding genes termed lpl. As the role lpl in virulence is still unclear, we deleted the entire lpl cluster in the community-acquired methicillin-resistant S. aureus (CA-MRSA) USA300 and found that the mutant was defective in stimulation of pro-inflammatory cytokines in human immune cells. Moreover, the major finding highlighted in this study is that the lpl cluster contributes to invasion into non-professional phagocytes such as epithelial cells and keratinocytes. Furthermore, the lpl-dependent increase in invasive activity, most likely, accounts for the enhanced bacterial burden observed in a murine kidney abscess model. In general, internalization of a pathogen into host epithelial cells shields the pathogen from immune defense and antibiotic treatment. However, further investigation is needed to clarify whether the increased ability to invade host cells is responsible for the potent disseminative activity and hypervirulent phenotype characterizing the νSaα type I island expressing S. aureus strains, including the USA300 CA-MRSA strain.
Zdroje
1. Stoll H, Dengjel J, Nerz C, Götz F (2005) Staphylococcus aureus deficient in lipidation of prelipoproteins is attenuated in growth and immune activation. Infect Immun 73: 2411–2423. 15784587
2. Hashimoto M, Tawaratsumida K, Kariya H, Aoyama K, Tamura T, et al. (2006) Lipoprotein is a predominant Toll-like receptor 2 ligand in Staphylococcus aureus cell wall components. IntImmunol 18: 355–362. 16373361
3. Parcina M, Wendt C, Götz F, Zawatzky R, Zähringer U, et al. (2008) Staphylococcus aureus-induced plasmacytoid dendritic cell activation is based on an IgG-mediated memory response. J Immunol 181: 3823–3833. 18768836
4. Nielsen JB, Lampen JO (1982) Membrane-bound penicillinases in Gram-positive bacteria. J Biol Chem 257: 4490–4495. 6802832
5. Sibbald MJ, Ziebandt AK, Engelmann S, Hecker M, de Jong A, et al. (2006) Mapping the pathways to staphylococcal pathogenesis by comparative secretomics. Microbiol Mol Biol Rev 70: 755–788. 16959968
6. Schmaler M, Jann NJ, Ferracin F, Landolt LZ, Biswas L, et al. (2009) Lipoproteins in Staphylococcus aureus mediate inflammation by TLR2 and iron-dependent growth in vivo. J Immunol 182: 7110–7118. doi: 10.4049/jimmunol.0804292 19454708
7. Tsuru T, Kobayashi I (2008) Multiple genome comparison within a bacterial species reveals a unit of evolution spanning two adjacent genes in a tandem paralog cluster. MolBiolEvol 25: 2457–2473.
8. Baba T, Bae T, Schneewind O, Takeuchi F, Hiramatsu K (2008) Genome sequence of Staphylococcus aureus strain Newman and comparative analysis of staphylococcal genomes: polymorphism and evolution of two major pathogenicity islands. J Bacteriol 190: 300–310. 17951380
9. Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, et al. (2006) Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet 367: 731–739. 16517273
10. Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H, et al. (2001) Whole genome sequencing of methicillin-resistant Staphylococcus aureus. Lancet 357: 1225–1240. 11418146
11. Biswas L, Biswas R, Nerz C, Ohlsen K, Schlag M, et al. (2009) Role of the twin-arginine translocation pathway in Staphylococcus. J Bacteriol 191: 5921–5929. doi: 10.1128/JB.00642-09 19633084
12. Babu MM, Priya ML, Selvan AT, Madera M, Gough J, et al. (2006) A database of bacterial lipoproteins (DOLOP) with functional assignments to predicted lipoproteins. J Bacteriol 188: 2761–2773. 16585737
13. Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, et al. (2002) The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc Natl Acad Sci U S A 99: 7687–7692. 12032344
14. Cockfield JD, Pathak S, Edgeworth JD, Lindsay JA (2007) Rapid determination of hospital-acquired meticillin-resistant Staphylococcus aureus lineages. J Med Microbiol 56: 614–619. 17446283
15. Robinson DA, Kearns AM, Holmes A, Morrison D, Grundmann H, et al. (2005) Re-emergence of early pandemic Staphylococcus aureus as a community-acquired meticillin-resistant clone. Lancet 365: 1256–1258. 15811459
16. Herbert S, Ziebandt AK, Ohlsen K, Schafer T, Hecker M, et al. (2010) Repair of global regulators in Staphylococcus aureus 8325 and comparative analysis with other clinical isolates. Infect Immun 78: 2877–2889. doi: 10.1128/IAI.00088-10 20212089
17. Rosenstein R, Götz F (2013) What distinguishes highly pathogenic staphylococci from medium- and non-pathogenic? Curr Top Microbiol Immunol 358: 33–89. doi: 10.1007/82_2012_286 23224647
18. Hilmi D, Parcina M, Bode K, Ostrop J, Schuett S, et al. (2013) Functional variation reflects intra-strain diversity of Staphylococcus aureus small colony variants in the host-pathogen interaction. Int J Med Microbiol 303: 61–69. doi: 10.1016/j.ijmm.2012.12.008 23375466
19. Strommenger B, Bartels MD, Kurt K, Layer F, Rohde SM, et al. (2014) Evolution of methicillin-resistant Staphylococcus aureus towards increasing resistance. J Antimicrob Chemother 69: 616–622. doi: 10.1093/jac/dkt413 24150844
20. Aliprantis AO, Yang RB, Mark MR, Suggett S, Devaux B, et al. (1999) Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science 285: 736–739. 10426996
21. Brightbill HD, Libraty DH, Krutzik SR, Yang RB, Belisle JT, et al. (1999) Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285: 732–736. 10426995
22. Buwitt-Beckmann U, Heine H, Wiesmüller KH, Jung G, Brock R, et al. (2006) TLR1- and TLR6-independent recognition of bacterial lipopeptides. J Biol Chem 281: 9049–9057. 16455646
23. Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, et al. (2007) Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 130: 1071–1082. 17889651
24. Takeda K, Takeuchi O, Akira S (2002) Recognition of lipopeptides by Toll-like receptors. J Endotoxin Res 8: 459–463. 12697090
25. Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, et al. (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 13: 933–940. 11431423
26. Hashimoto M, Tawaratsumida K, Kariya H, Kiyohara A, Suda Y, et al. (2006) Not lipoteichoic acid but lipoproteins appear to be the dominant immunobiologically active compounds in Staphylococcus aureus. J Immunol 177: 3162–3169. 16920954
27. Müller P, Müller-Anstett M, Wagener J, Gao Q, Kaesler S, et al. (2010) The Staphylococcus aureus lipoprotein SitC colocalizes with Toll-like receptor 2 (TLR2) in murine keratinocytes and elicits intracellular TLR2 accumulation. InfectImmun 78: 4243–4250. doi: 10.1128/IAI.00538-10 20679445
28. Schäffler H, Demircioglu DD, Kuhner D, Menz S, Bender A, et al. (2014) NOD2 stimulation by Staphylococcus aureus-derived peptidoglycan is boosted by Toll-Like Receptor 2 costimulation with lipoproteins in Dendritic Cells. Infect Immun 82: 4681–4688. doi: 10.1128/IAI.02043-14 25156723
29. Bassford PJ Jr., Silhavy TJ, Beckwith JR (1979) Use of gene fusion to study secretion of maltose-binding protein into Escherichia coli periplasm. J Bacteriol 139: 19–31. 110778
30. Müller-Anstett MA, Müller P, Albrecht T, Nega M, Wagener J, et al. (2010) Staphylococcal peptidoglycan co-localizes with Nod2 and TLR2 and activates innate immune response via both receptors in primary murine keratinocytes. PLoS One 5: e13153. doi: 10.1371/journal.pone.0013153 20949035
31. Wright JA, Nair SP (2010) Interaction of staphylococci with bone. Int J Med Microbiol 300: 193–204. doi: 10.1016/j.ijmm.2009.10.003 19889575
32. Menzies BE, Kourteva I (1998) Internalization of Staphylococcus aureus by endothelial cells induces apoptosis. Infect Immun 66: 5994–5998. 9826383
33. Ogawa SK, Yurberg ER, Hatcher VB, Levitt MA, Lowy FD (1985) Bacterial adherence to human endothelial cells in vitro. Infect Immun 50: 218–224. 4044035
34. Sinha B, Francois PP, Nusse O, Foti M, Hartford OM, et al. (1999) Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin alpha5beta1. Cell Microbiol 1: 101–117. 11207545
35. Bayles KW, Wesson CA, Liou LE, Fox LK, Bohach GA, et al. (1998) Intracellular Staphylococcus aureus escapes the endosome and induces apoptosis in epithelial cells. Infect Immun 66: 336–342. 9423876
36. Dziewanowska K, Patti JM, Deobald CF, Bayles KW, Trumble WR, et al. (1999) Fibronectin binding protein and host cell tyrosine kinase are required for internalization of Staphylococcus aureus by epithelial cells. Infect Immun 67: 4673–4678. 10456915
37. Usui A, Murai M, Seki K, Sakurada J, Masuda S (1992) Conspicuous ingestion of Staphylococcus aureus organisms by murine fibroblasts in vitro. Microbiol Immunol 36: 545–550. 1513269
38. Ellington JK, Reilly SS, Ramp WK, Smeltzer MS, Kellam JF, et al. (1999) Mechanisms of Staphylococcus aureus invasion of cultured osteoblasts. Microb Pathog 26: 317–323. 10343060
39. Jevon M, Guo C, Ma B, Mordan N, Nair SP, et al. (1999) Mechanisms of internalization of Staphylococcus aureus by cultured human osteoblasts. Infect Immun 67: 2677–2681. 10225942
40. Fowler T, Wann ER, Joh D, Johansson S, Foster TJ, et al. (2000) Cellular invasion by Staphylococcus aureus involves a fibronectin bridge between the bacterial fibronectin-binding MSCRAMMs and host cell beta1 integrins. Eur J Cell Biol 79: 672–679. 11089915
41. Dziewanowska K, Carson AR, Patti JM, Deobald CF, Bayles KW, et al. (2000) Staphylococcal fibronectin binding protein interacts with heat shock protein 60 and integrins: role in internalization by epithelial cells. Infect Immun 68: 6321–6328. 11035741
42. Haggar A, Hussain M, Lonnies H, Herrmann M, Norrby-Teglund A, et al. (2003) Extracellular adherence protein from Staphylococcus aureus enhances internalization into eukaryotic cells. Infect Immun 71: 2310–2317. 12704099
43. Hirschhausen N, Schlesier T, Schmidt MA, Götz F, Peters G, et al. (2010) A novel staphylococcal internalization mechanism involves the major autolysin Atl and heat shock cognate protein Hsc70 as host cell receptor. Cell Microbiol.
44. Rosenstein R, Nerz C, Biswas L, Resch A, Raddatz G, et al. (2009) Genome analysis of the meat starter culture bacterium Staphylococcus carnosus TM300. Appl Environ Microbiol 75: 811–822. doi: 10.1128/AEM.01982-08 19060169
45. Albrecht T, Raue S, Rosenstein R, Nieselt K, Götz F (2012) Phylogeny of the staphylococcal major autolysin and its use in genus and species typing. J Bacteriol 194: 2630–2636. doi: 10.1128/JB.06609-11 22427631
46. Nestle FO, Di Meglio P, Qin JZ, Nickoloff BJ (2009) Skin immune sentinels in health and disease. Nat Rev Immunol 9: 679–691. doi: 10.1038/nri2622 19763149
47. Mauthe M, Yu W, Krut O, Krönke M, Götz F, et al. (2012) WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation. Int J Cell Biol 2012: 179207. doi: 10.1155/2012/179207 22829830
48. Löffler B, Tuchscherr L, Niemann S, Peters G (2014) Staphylococcus aureus persistence in non-professional phagocytes. Int J Med Microbiol 304: 170–176. doi: 10.1016/j.ijmm.2013.11.011 24365645
49. Zhang W, Bielaszewska M, Kunsmann L, Mellmann A, Bauwens A, et al. (2013) Lability of the pAA Virulence Plasmid in O104:H4: Implications for Virulence in Humans. PLoS One 8: e66717. 23805269
50. Karch H, Denamur E, Dobrindt U, Finlay BB, Hengge R, et al. (2012) The enemy within us: lessons from the 2011 European Escherichia coli O104:H4 outbreak. EMBO Mol Med 4: 841–848. doi: 10.1002/emmm.201201662 22927122
51. Pizarro-Cerda J, Kuhbacher A, Cossart P (2012) Entry of Listeria monocytogenes in mammalian epithelial cells: an updated view. Cold Spring Harb Perspect Med 2.
52. Brückner R (1997) Gene replacement in Staphylococcus carnosus and Staphylococcus xylosus. FEMS MicrobiolLett 151: 1–8.
53. Leibig M, Krismer B, Kolb M, Friede A, Götz F, et al. (2008) Marker removal in staphylococci via Cre recombinase and different lox sites. ApplEnvironMicrobiol 74: 1316–1323. doi: 10.1055/s-2008-1081293 18622904
54. Peschel A, Götz F (1996) Analysis of the Staphylococcus epidermidis genes epiF,-E, and-G involved in epidermin immunity. J Bacteriol 178: 531–536. 8550476
55. Götz F, Schumacher B (1987) Improvements of protoplast transformation in Staphylococcus carnosus. Fems Microbiology Letters 40: 285–288.
56. Wieland KP, Wieland B, Götz F (1995) A promoter-screening plasmid and xylose-inducible, glucose-repressible expression vectors for Staphylococcus carnosus. Gene 158: 91–96. 7789818
57. Fic E, Kedracka-Krok S, Jankowska U, Pirog A, Dziedzicka-Wasylewska M (2010) Comparison of protein precipitation methods for various rat brain structures prior to proteomic analysis. Electrophoresis 31: 3573–3579. doi: 10.1002/elps.201000197 20967768
58. Ziegler-Heitbrock HW, Schraut W, Wendelgass P, Strobel M, Sternsdorf T, et al. (1994) Distinct patterns of differentiation induced in the monocytic cell line Mono Mac 6. J Leukoc Biol 55: 73–80. 8283142
59. Bekeredjian-Ding I, Roth SI, Gilles S, Giese T, Ablasser A, et al. (2006) T cell-independent, TLR-induced IL-12p70 production in primary human monocytes. J Immunol 176: 7438–7446. 16751389
60. Wanke I, Skabytska Y, Kraft B, Peschel A, Biedermann T, et al. (2013) Staphylococcus aureus skin colonization is promoted by barrier disruption and leads to local inflammation. Exp Dermatol 22: 153–155. doi: 10.1111/exd.12083 23362876
61. Meier F, Nesbit M, Hsu MY, Martin B, Van Belle P, et al. (2000) Human melanoma progression in skin reconstructs: biological significance of bFGF. Am J Pathol 156: 193–200. 10623667
62. Hahn BL, Onunkwo CC, Watts CJ, Sohnle PG (2009) Systemic dissemination and cutaneous damage in a mouse model of staphylococcal skin infections. Microb Pathog 47: 16–23. doi: 10.1016/j.micpath.2009.04.007 19397991
63. Kraus B, Boller K, Reuter A, Schnierle BS (2011) Characterization of the human endogenous retrovirus K Gag protein: identification of protease cleavage sites. Retrovirology 8: 21. doi: 10.1186/1742-4690-8-21 21429186
64. Gelderblom HR, Hausmann EH, Ozel M, Pauli G, Koch MA (1987) Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins. Virology 156: 171–176. 3643678
65. Saising J, Dube L, Ziebandt AK, Voravuthikunchai SP, Nega M, et al. (2012) Activity of gallidermin on Staphylococcus aureus and Staphylococcus epidermidis biofilms. Antimicrob Agents Chemother 56: 5804–5810. doi: 10.1128/AAC.01296-12 22926575
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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