#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

BdlA, DipA and Induced Dispersion Contribute to Acute Virulence and Chronic Persistence of


Pathogenic bacteria, including the human pathogen Pseudomonas aeruginosa, can cause acute and chronic infections. The difference in these infection modes can be explained by how bacteria grow. Acute infections occur when individual bacteria rapidly replicate, produce high levels of virulence factors, and disseminate from the nidus of infection. Chronic infections occur when bacteria adhere to tissue or implanted medical devices and form multi-cellular, matrix-encased aggregates known as biofilms. The acute-to-chronic infection switch occurs when bacteria transition from planktonic to biofilm growth. However, the contribution of dispersion, the process by which bacteria leave a biofilm to return to planktonic growth, remains unclear. Here, we demonstrate that, while having left a biofilm, dispersed cells are distinct from planktonic cells with respect to gene expression, release of matrix-degrading enzymes, and pathogenicity. We found that a mutant impaired in nutrient-induced dispersion, while enhancing chronic infections, is impaired in mounting acute infections in both plant and mouse hosts. Overall, this work establishes that dispersed cells have a unique virulence phenotype, with nutrient-induced dispersion not only serving as an integral part of both acute and chronic infections but also as a potential mechanism of infection control.


Vyšlo v časopise: BdlA, DipA and Induced Dispersion Contribute to Acute Virulence and Chronic Persistence of. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004168
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004168

Souhrn

Pathogenic bacteria, including the human pathogen Pseudomonas aeruginosa, can cause acute and chronic infections. The difference in these infection modes can be explained by how bacteria grow. Acute infections occur when individual bacteria rapidly replicate, produce high levels of virulence factors, and disseminate from the nidus of infection. Chronic infections occur when bacteria adhere to tissue or implanted medical devices and form multi-cellular, matrix-encased aggregates known as biofilms. The acute-to-chronic infection switch occurs when bacteria transition from planktonic to biofilm growth. However, the contribution of dispersion, the process by which bacteria leave a biofilm to return to planktonic growth, remains unclear. Here, we demonstrate that, while having left a biofilm, dispersed cells are distinct from planktonic cells with respect to gene expression, release of matrix-degrading enzymes, and pathogenicity. We found that a mutant impaired in nutrient-induced dispersion, while enhancing chronic infections, is impaired in mounting acute infections in both plant and mouse hosts. Overall, this work establishes that dispersed cells have a unique virulence phenotype, with nutrient-induced dispersion not only serving as an integral part of both acute and chronic infections but also as a potential mechanism of infection control.


Zdroje

1. GoodmanAL, KulasekaraB, RietschA, BoydD, SmithRS, et al. (2004) A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa. Dev Cell 7: 745–754.

2. VentreI, GoodmanAL, Vallet-GelyI, VasseurP, SosciaC, et al. (2006) Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes. Proc Natl Acad Sci 103: 171–176.

3. LaskowskiMA, KazmierczakBI (2006) Mutational Analysis of RetS, an Unusual Sensor Kinase-Response Regulator Hybrid Required for Pseudomonas aeruginosa Virulence. Infect Immun 74: 4462–4473.

4. PetrovaOE, SauerK (2010) The novel two-component regulatory system BfiSR regulates biofilm development by controlling the small RNA rsmZ through CafA. J Bacteriol 192: 5275–5288.

5. PetrovaOE, SauerK (2011) SagS contributes to the motile-sessile switch and acts in concert with BfiSR to enable Pseudomonas aeruginosa biofilm formation J Bacteriol. 193: 6614–6628.

6. EmoriTG, GaynesRP (1993) An overview of nosocomial infections, including the role of the microbiology laboratory. Clin Microbiol Rev 6: 428–442.

7. CostertonJW, StewartPS, GreenbergEP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284: 1318–1322.

8. KuchmaSL, ConnollyJP, O'TooleGA (2005) A three-component regulatory system regulates biofilm maturation and type III secretion in Pseudomonas aeruginosa. J Bacteriol 187: 1441–1454.

9. YahrTL, GreenbergEP (2004) The Genetic Basis for the Commitment to Chronic versus Acute Infection in Pseudomonas aeruginosa. Molecular Cell 16: 497–498.

10. SuS, HassettDJ (2012) Anaerobic Pseudomonas aeruginosa and other obligately anaerobic bacterial biofilms growing in the thick airway mucus of chronically infected cystic fibrosis patients: an emerging paradigm or “Old Hat”? Expert Opin Ther Targets 16: 859–873.

11. GilliganPH (1991) Microbiology of airway disease in patients with cystic fibrosis. Clin Microbiol Rev 4: 35–51.

12. GovanJR, DereticV (1996) Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol Rev 60: 539–574.

13. DonlanRM, CostertonJW (2002) Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms. Clin Microbiol Rev 15: 167–193.

14. WagnerV, IglewskiB (2008) P. aeruginosa biofilms in CF Infection. Clin Rev Allergy Immunol 35: 124–134.

15. PruittJBA, McManusAT, KimSH, GoodwinCW (1998) Burn Wound Infections: Current Status. World Journal of Surgery 22: 135–145.

16. FleiszigSM, EvansDJ (2002) The pathogenesis of bacterial keratitis: studies with Pseudomonas aeruginosa. Clin Exp Optom 85: 271–278.

17. TakeyamaK, KunishimaY, MatsukawaM, TakahashiS, HiroseT, et al. (2002) Multidrug-resistant Pseudomonas aeruginosa isolated from the urine of patients with urinary tract infection. J Infect Chemother 8: 58–63.

18. ReinhardtA, KohlerT, WoodP, RohnerP, DumasJ-L, et al. (2007) Development and Persistence of Antimicrobial Resistance in Pseudomonas aeruginosa: a Longitudinal Observation in Mechanically Ventilated Patients. Antimicrob Agents Chemother 51: 1341–1350.

19. CostertonJW, LewandowskiZ, CaldwellDE, KorberDR, Lappin-ScottHM (1995) Microbial biofilms. Annu Rev Microbiol 49: 711–745.

20. GooderhamWJ, HancockREW (2009) Regulation of virulence and antibiotic resistance by two-component regulatory systems in Pseudomonas aeruginosa. FEMS Microbiol Rev 33: 279–294.

21. PetrovaOE, SchurrJR, SchurrMJ, SauerK (2011) The novel Pseudomonas aeruginosa two-component regulator BfmR controls bacteriophage-mediated lysis and DNA release during biofilm development through PhdA. Mol Microbiol 81: 767–783.

22. PetrovaOE, SchurrJR, SchurrMJ, SauerK (2012) Microcolony formation by the opportunistic pathogen Pseudomonas aeruginosa requires pyruvate and pyruvate fermentation. Mol Microbiol 86: 819–835.

23. LaskowskiMA, OsbornE, KazmierczakBI (2004) A novel sensor kinase–response regulator hybrid regulates type III secretion and is required for virulence in Pseudomonas aeruginosa. Mol Microbiol 54: 1090–1103.

24. ZolfagharI, AngusAA, KangPJ, ToA, EvansDJ, et al. (2005) Mutation of retS, encoding a putative hybrid two-component regulatory protein in Pseudomonas aeruginosa, attenuates multiple virulence mechanisms. Microbes Infect 7: 1305–1316.

25. HolderIA, NeelyAN, FrankDW (2001) Type III secretion/intoxication system important in virulence of Pseudomonas aeruginosa infections in burns. Burns 27: 129–130.

26. SmithRS, WolfgangMC, LoryS (2004) An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia. Infect Immun 72: 1677–1684.

27. von GotzF, HausslerS, JordanD, SaravanamuthuSS, WehmhonerD, et al. (2004) Expression analysis of a highly adherent and cytotoxic small colony variant of Pseudomonas aeruginosa isolated from a lung of a patient with cystic fibrosis. J Bacteriol 186: 3837–3847.

28. MikkelsenH, BondNJ, SkindersoeME, GivskovM, LilleyKS, et al. (2009) Biofilms and type III secretion are not mutually exclusive in Pseudomonas aeruginosa. Microbiology 155: 687–798.

29. GallagherLA, ManoilC (2001) Pseudomonas aeruginosa PAO1 Kills Caenorhabditis elegans by Cyanide Poisoning. J Bacteriol 183: 6207–6214.

30. CartersonAJ, MoriciLA, JacksonDW, FriskA, LizewskiSE, et al. (2004) The transcriptional regulator AlgR controls cyanide production in Pseudomonas aeruginosa. J Bacteriol 186: 6837–6844.

31. FoldersJ, AlgraJ, RoelofsMS, van LoonLC, TommassenJ, et al. (2001) Characterization of Pseudomonas aeruginosa Chitinase, a Gradually Secreted Protein. J Bacteriol 183: 7044–7052.

32. ElsheikhLE, KroneviT, WretlindB, AbaasS, IglewskiBH (1987) Assessment of elastase as a Pseudomonas aeruginosa virulence factor in experimental lung infection in mink. Veterinary Microbiology 13: 281–289.

33. Mahajan-MiklosS, TanM-W, RahmeLG, AusubelFM (1999) Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96: 47–56.

34. McClureCD, SchillerNL (1996) Inhibition of Macrophage Phagocytosis by Pseudomonas aeruginosa Rhamnolipids In Vitro and In Vivo. Current Microbiology 33: 109–117.

35. JensenPØ, BjarnsholtT, PhippsR, RasmussenTB, CalumH, et al. (2007) Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa. Microbiology 153: 1329–1338.

36. SauerK, CullenMC, RickardAH, ZeefLAH, DaviesDG, et al. (2004) Characterization of nutrient-induced dispersion in Pseudomonas aeruginosa PAO1 biofilm. J Bacteriol 186: 7312–7326.

37. SauerK, CamperAK, EhrlichGD, CostertonJW, DaviesDG (2002) Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm. J Bacteriol 184: 1140–1154.

38. GjermansenM, RagasP, SternbergC, MolinS, Tolker-NielsenT (2005) Characterization of starvation-induced dispersion in Pseudomonas putida biofilms. Environ Microbiol 7: 894–904.

39. KaplanJB, RagunathC, VelliyagounderK, FineDH, RamasubbuN (2004) Enzymatic detachment of Staphylococcus epidermidis biofilms. Antimicrob Agents Chemother 48: 2633–2636.

40. LeeSF, LiYH, BowdenGH (1996) Detachment of Streptococcus mutans biofilm cells by an endogenous enzymatic activity. Infection and Immunity 64: 1035–1038.

41. GjermansenM, NilssonM, YangL, Tolker-NielsenT (2010) Characterization of starvation-induced dispersion in Pseudomonas putida biofilms: genetic elements and molecular mechanisms. Mol Microbiol 75: 815–826.

42. HinsaSM, Espinosa-UrgelM, RamosJL, O'TooleGA (2003) Transition from reversible to irreversible attachment during biofilm formation by Pseudomonas fluorescens WCS365 requires an ABC transporter and a large secreted protein. Mol Microbiol 49: 905–918.

43. MondsRD, NewellPD, GrossRH, O'TooleGA (2007) Phosphate-dependent modulation of c-di-GMP levels regulates Pseudomonas fluorescens Pf0-1 biofilm formation by controlling secretion of the adhesin LapA. Mol Microbiol 63: 656–679.

44. WebbJS, ThompsonLS, JamesS, CharltonT, Tolker-NielsenT, et al. (2003) Cell death in Pseudomonas aeruginosa biofilm development. J Bacteriol 185: 4585–4592.

45. PetrovaOE, SauerK (2012) Dispersion by Pseudomonas aeruginosa requires an unusual posttranslational modification of BdlA. Proc National Acad Sci 109: 16690–16695.

46. Basu RoyA, PetrovaOE, SauerK (2012) The phosphodiesterase DipA (PA5017) is essential for Pseudomonas aeruginosa biofilm dispersion. J Bacteriol 194: 2904–2915.

47. DaviesDG, MarquesCNH (2009) A fatty acid messenger is responsible for inducing dispersion in microbial biofilms. J Bacteriol 191: 1393–1403.

48. LiY, HeineS, EntianM, SauerK, Frankenberg-DinkelN (2013) NO-induced biofilm dispersion in Pseudomonas aeruginosa is mediated by a MHYT-domain coupled phosphodiesterase. J Bacteriol 195: 3531–3542.

49. ThormannKM, SavilleRM, ShuklaS, SpormannAM (2005) Induction of rapid detachment in Shewanella oneidensis MR-1 biofilms. J Bacteriol 187: 1014–1021.

50. ApplegateDH, BryersJD (1991) Effects on carbon and oxygen limitations and calcium concentrations on biofilm removal processes Biotechnol Bioeng. 37: 17–25.

51. BarraudN, HassettDJ, HwangS-H, RiceSA, KjellebergS, et al. (2006) Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa. J Bacteriol 188: 7344–7353.

52. CotterPA, StibitzS (2007) c-di-GMP-mediated regulation of virulence and biofilm formation. Curr Opin Microbiol 10: 17–23.

53. D'ArgenioDA, MillerSI (2004) Cyclic di-GMP as a bacterial second messenger. Microbiology 150: 2497–2502.

54. ThormannKM, DuttlerS, SavilleRM, HyodoM, ShuklaS, et al. (2006) Control of formation and cellular detachment from Shewanella oneidensis MR-1 biofilms by cyclic di-GMP. J Bacteriol 188: 2681–2691.

55. AnS, WuJe, ZhangL-H (2010) Modulation of Pseudomonas aeruginosa biofilm dispersal by a cyclic-di-GMP phosphodiesterase with a putative hypoxia-sensing fomain. Appl Environ Microbiol 76: 8160–8173.

56. MorganR, KohnS, HwangS-H, HassettDJ, SauerK (2006) BdlA, a chemotaxis regulator essential for biofilm dispersion in Pseudomonas aeruginosa. J Bacteriol 188: 7335–7343.

57. BarraudN, SchleheckD, KlebensbergerJ, WebbJS, HassettDJ, et al. (2009) Nitric oxide signaling in Pseudomonas aeruginosa biofilms mediates phosphodiesterase activity, decreased cyclic di-GMP levels, and enhanced dispersal. J Bacteriol 191: 7333–7342.

58. PetrovaOE, SauerK (2012) PAS domain residues and prosthetic group involved in BdlA-dependent dispersion response by Pseudomonas aeruginosa biofilms. J Bacteriol 194: 5817–5828.

59. DowJM, FouhyY, LuceyJF, RyanRP (2006) The HD-GYP domain, cyclic di-GMP signaling, and bacterial virulence to plants. Mol Plant Microbe Interact 19: 1378–1384.

60. KulasekaraH, LeeV, BrencicA, LiberatiN, UrbachJ, et al. (2006) Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence. Proc Natl Acad Sci 103: 2839–2844.

61. ChristensenLD, van GennipM, RybtkeMT, WuH, ChiangW-C, et al. (2013) Clearance of Pseudomonas aeruginosa foreign-body biofilm infections through reduction of the cyclic di-GMP level in the bacteria. Infect Immun 81: 2705–2713.

62. FlemmingH-C, NeuTR, WozniakDJ (2007) The EPS matrix: the “house of biofilm cells”. J Bacteriol 189: 7945–7947.

63. FlemmingHC, WingenderJ (2010) The biofilm matrix. Nat Rev Microbiol 8: 623–633.

64. RyderC, ByrdM, WozniakDJ (2007) Role of polysaccharides in Pseudomonas aeruginosa biofilm development. Curr Opin Microbiol 10: 644–648.

65. ArmstrongS, YatesSP, MerrillAR (2002) Insight into the Catalytic Mechanism of Pseudomonas aeruginosa Exotoxin A. Journal of Biological Chemistry 277: 46669–46675.

66. WagnerVE, BushnellD, PassadorL, BrooksAI, IglewskiBH (2003) Microarray Analysis of Pseudomonas aeruginosa Quorum-Sensing Regulons: Effects of Growth Phase and Environment. J Bacteriol 185: 2080–2095.

67. HentzerM, WuH, AndersenJB, RiedelK, RasmussenTB, et al. (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22: 3803–3815.

68. RahmeLG, TanM-W, LeL, WongSM, TompkinsRG, et al. (1997) Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors. Proc Natl Acad Sci 94: 13245–13250.

69. RahmeLG, StevensEJ, WolfortSF, ShaoJ, TompkinsRG, et al. (1995) Common virulence factors for bacterial pathogenicity in plants and animals. Science 268: 1899–1902.

70. LauGW, RanH, KongF, HassettDJ, MavrodiD (2004) Pseudomonas aeruginosa Pyocyanin Is Critical for Lung Infection in Mice. Infect Immun 72: 4275–4278.

71. YoonSS, CoakleyR, LauGW, LymarSV, GastonB, et al. (2006) Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions. J Clin Invest 116: 436–446.

72. CashHD, WoodsDE, McColloughB, W.GJ, BassJA (1979) A rat model of chronic respiratory infection with Pseudomonas aeruginosa. Am Rev Respir Dis 119: 453–459.

73. LauGW, BritiganBE, HassettDJ (2005) Pseudomonas aeruginosa OxyR Is Required for Full Virulence in Rodent and Insect Models of Infection and for Resistance to Human Neutrophils. Infect Immun 73: 2550–2553.

74. Garcia-MedinaR, DunneWM, SinghPK, BrodySL (2005) Pseudomonas aeruginosa acquires biofilm-like properties within airway epithelial cells. Infect Immun 73: 8298–8305.

75. WoodsDE, CantinA, CooleyJ, KenneyDM, Remold-O'DonnellE (2005) Aerosol treatment with MNEI suppresses bacterial proliferation in a model of chronic Pseudomonas aeruginosa lung infection. Pediatr Pulmonol 39: 141–149.

76. HickmanJW, TifreaDF, HarwoodCS (2005) A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels. Proc Natl Acad Sci 102: 14422–14427.

77. CostertonJW, StewartPS, GreenbergEP (1999) Bacterial Biofilms: A Common Cause of Persistent Infections. Science 284: 1318–1322.

78. PearsonJP, FeldmanM, IglewskiBH, PrinceA (2000) Pseudomonas aeruginosa cell-to-cell signaling is required for virulence in a model of acute pulmonary infection. Infect Immun 68: 4331–4334.

79. TangH, KaysM, PrinceA (1995) Role of Pseudomonas aeruginosa pili in acute pulmonary infection. Infect Immun 63: 1278–1285.

80. StoodleyP, SauerK, DaviesDG, CostertonJW (2002) Biofilms as complex differentiated communities. Annu Rev Microbiol 56: 187–209.

81. DonaldsonSH, BennettWD, ZemanKL, KnowlesMR, TarranR, et al. (2006) Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med 354: 241–250.

82. SauerK, CamperAK (2001) Characterization of phenotypic changes in Pseudomonas putida in response to surface-associated growth. J Bacteriol 183: 6579–6589.

83. PetersonGL (1977) A simplification of the protein assay method of Lowry, et al. which is more generally applicable. Anal Biochem 83: 346–356.

84. Southey-PilligCJ, DaviesDG, SauerK (2005) Characterization of temporal protein production in Pseudomonas aeruginosa biofilms. J Bacteriol 187: 8114–8126.

85. PetrovaOE, SauerK (2009) A novel signaling network essential for regulating Pseudomonas aeruginosa biofilm development. PLoS Pathog 5: e1000668.

86. ByrdMS, SadovskayaI, VinogradovE, LuH, SprinkleAB, et al. (2009) Genetic and biochemical analyses of the Pseudomonas aeruginosa Psl exopolysaccharide reveal overlapping roles for polysaccharide synthesis enzymes in Psl and LPS production. Mol Microbiol 73: 622–638.

87. SinicropiD, BakerDL, PrinceWS, ShifferK, ShakS (1994) Colorimetric determination of DNase I activity with a DNA-methyl green substrate. Anal Biochem 222: 351–358.

88. AllegrucciM, SauerK (2007) Characterization of colony morphology variants isolated from Streptococcus pneumoniae biofilms. J Bacteriol 189: 2030–2038.

89. AllegrucciM, SauerK (2008) Formation of Streptococcus pneumoniae non-phase-variable colony variants is due to increased mutation frequency present under biofilm growth conditions. J Bacteriol 190: 6330–6339.

90. McBainAJ, BartoloRG, CatrenichCE, CharbonneauD, LedderRG, et al. (2003) Microbial characterization of biofilms in domestic drains and the establishment of stable biofilm microcosms. Appl Environ Microbiol 69: 177–185.

91. StarkeyM, RahmeLG (2009) Modeling Pseudomonas aeruginosa pathogenesis in plant hosts. Nat Protocols 4: 117–124.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 6
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#