A Novel Signal Transduction Pathway that Modulates Quorum Sensing and Bacterial Virulence in
The rhl quorum-sensing (QS) system allows P. aeruginosa to regulate diverse metabolic adaptations and virulence. However, how rhl QS system is regulated remains largely unknown. Here, we report that two-component sensor BfmS controls rhl QS system by repressing its cognate response regulator BfmR, which directly suppresses the expression of rhl QS regulator RhlR gene and reduces the production of QS signal molecule N-butanoyl-L-homoserine lactone (C4-HSL). We find that BfmS is critical to the ability of P. aeruginosa to modulate the expression of virulence-associated traits and adapt to the host. Intriguingly, although wild-type BfmS is a repressor of BfmR, naturally occurring missense mutation (L181P, L181P/E376Q, or R393H) can convert its function from a repressor to an activator of BfmR, leading to BfmR activation, which in turn reduces the level of rhl QS signal C4-HSL. These results, therefore, provide important and novel insight into the regulation and evolution of P. aeruginosa virulence.
Vyšlo v časopise:
A Novel Signal Transduction Pathway that Modulates Quorum Sensing and Bacterial Virulence in. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004340
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004340
Souhrn
The rhl quorum-sensing (QS) system allows P. aeruginosa to regulate diverse metabolic adaptations and virulence. However, how rhl QS system is regulated remains largely unknown. Here, we report that two-component sensor BfmS controls rhl QS system by repressing its cognate response regulator BfmR, which directly suppresses the expression of rhl QS regulator RhlR gene and reduces the production of QS signal molecule N-butanoyl-L-homoserine lactone (C4-HSL). We find that BfmS is critical to the ability of P. aeruginosa to modulate the expression of virulence-associated traits and adapt to the host. Intriguingly, although wild-type BfmS is a repressor of BfmR, naturally occurring missense mutation (L181P, L181P/E376Q, or R393H) can convert its function from a repressor to an activator of BfmR, leading to BfmR activation, which in turn reduces the level of rhl QS signal C4-HSL. These results, therefore, provide important and novel insight into the regulation and evolution of P. aeruginosa virulence.
Zdroje
1. StoverCK, PhamXQ, ErwinAL, MizoguchiSD, WarrenerP, et al. (2000) Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406: 959–964.
2. National Nosocomial Infections Surveillance S (2004) National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 32: 470–485.
3. LyczakJB, CannonCL, PierGB (2002) Lung infections associated with cystic fibrosis. Clin Microbiol Rev 15: 194–222.
4. SmithRS, IglewskiBH (2003) P. aeruginosa quorum-sensing systems and virulence. Curr Opin Microbiol 6: 56–60.
5. WilliamsP, CamaraM (2009) Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr Opin Microbiol 12: 182–191.
6. JimenezPN, KochG, ThompsonJA, XavierKB, CoolRH, et al. (2012) The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol Mol Biol Rev 76: 46–65.
7. GooderhamWJ, HancockRE (2009) Regulation of virulence and antibiotic resistance by two-component regulatory systems in Pseudomonas aeruginosa. FEMS Microbiol Rev 33: 279–294.
8. BalasubramanianD, SchneperL, KumariH, MatheeK (2013) A dynamic and intricate regulatory network determines Pseudomonas aeruginosa virulence. Nucleic Acids Res 41: 1–20.
9. RutherfordST, BasslerBL (2012) Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med 2 doi: 10.1101/cshperspect.a012427
10. SchusterM, GreenbergEP (2006) A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa. Int J Med Microbiol 296: 73–81.
11. RodrigueA, QuentinY, LazdunskiA, MejeanV, FoglinoM (2000) Two-component systems in Pseudomonas aeruginosa: why so many? Trends Microbiol 8: 498–504.
12. RouxA, PayneSM, GilmoreMS (2009) Microbial telesensing: probing the environment for friends, foes, and food. Cell Host Microbe 6: 115–124.
13. DekimpeV, DezielE (2009) Revisiting the quorum-sensing hierarchy in Pseudomonas aeruginosa: the transcriptional regulator RhlR regulates LasR-specific factors. Microbiology 155: 712–723.
14. LeeJ, WuJ, DengY, WangJ, WangC, et al. (2013) A cell-cell communication signal integrates quorum sensing and stress response. Nat Chem Biol 9: 339–343.
15. Croda-GarciaG, Grosso-BecerraV, Gonzalez-ValdezA, Servin-GonzalezL, Soberon-ChavezG (2011) Transcriptional regulation of Pseudomonas aeruginosa rhlR: role of the CRP orthologue Vfr (virulence factor regulator) and quorum-sensing regulators LasR and RhlR. Microbiology 157: 2545–2555.
16. StockAM, RobinsonVL, GoudreauPN (2000) Two-component signal transduction. Annu Rev Biochem 69: 183–215.
17. ShilohMU, ManzanilloP, CoxJS (2008) Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection. Cell Host Microbe 3: 323–330.
18. TorresVJ, StauffDL, PishchanyG, BezbradicaJS, GordyLE, et al. (2007) A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence. Cell Host Microbe 1: 109–119.
19. DongYH, ZhangXF, AnSW, XuJL, ZhangLH (2008) A novel two-component system BqsS-BqsR modulates quorum sensing-dependent biofilm decay in Pseudomonas aeruginosa. Commun Integr Biol 1: 88–96.
20. ReimmannC, BeyelerM, LatifiA, WintelerH, FoglinoM, et al. (1997) The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. Mol Microbiol 24: 309–319.
21. JensenV, LonsD, ZaouiC, BredenbruchF, MeissnerA, et al. (2006) RhlR expression in Pseudomonas aeruginosa is modulated by the Pseudomonas quinolone signal via PhoB-dependent and -independent pathways. J Bacteriol 188: 8601–8606.
22. DieppoisG, DucretV, CailleO, PerronK (2012) The transcriptional regulator CzcR modulates antibiotic resistance and quorum sensing in Pseudomonas aeruginosa. PLoS One 7: e38148.
23. SonMS, MatthewsWJJr, KangY, NguyenDT, HoangTT (2007) In vivo evidence of Pseudomonas aeruginosa nutrient acquisition and pathogenesis in the lungs of cystic fibrosis patients. Infect Immun 75: 5313–5324.
24. 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.
25. PetrovaOE, SauerK (2009) A novel signaling network essential for regulating Pseudomonas aeruginosa biofilm development. PLoS Pathog 5: e1000668.
26. LanL, MurrayTS, KazmierczakBI, HeC (2010) Pseudomonas aeruginosa OspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection. Mol Microbiol 75: 76–91.
27. KohlerT, CurtyLK, BarjaF, van DeldenC, PechereJC (2000) Swarming of Pseudomonas aeruginosa is dependent on cell-to-cell signaling and requires flagella and pili. J Bacteriol 182: 5990–5996.
28. LiangH, DuanJ, SibleyCD, SuretteMG, DuanK (2011) Identification of mutants with altered phenazine production in Pseudomonas aeruginosa. J Med Microbiol 60: 22–34.
29. SchusterM, LostrohCP, OgiT, GreenbergEP (2003) Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J Bacteriol 185: 2066–2079.
30. OglesbyAG, FarrowJM3rd, LeeJH, TomarasAP, GreenbergEP, et al. (2008) The influence of iron on Pseudomonas aeruginosa physiology: a regulatory link between iron and quorum sensing. J Biol Chem 283: 15558–15567.
31. WolfeAJ (2005) The acetate switch. Microbiol Mol Biol Rev 69: 12–50.
32. FleiszigSM, ZaidiTS, PrestonMJ, GroutM, EvansDJ, et al. (1996) Relationship between cytotoxicity and corneal epithelial cell invasion by clinical isolates of Pseudomonas aeruginosa. Infect Immun 64: 2288–2294.
33. YuanK, HuangC, FoxJ, GaidM, WeaverA, et al. (2011) Elevated inflammatory response in caveolin-1-deficient mice with Pseudomonas aeruginosa infection is mediated by STAT3 protein and nuclear factor kappaB (NF-kappaB). J Biol Chem 286: 21814–21825.
34. GuoQ, ShenN, YuanK, LiJ, WuH, et al. (2012) Caveolin-1 plays a critical role in host immunity against Klebsiella pneumoniae by regulating STAT5 and Akt activity. Eur J Immunol 42: 1500–1511.
35. LiX, ZhouX, YeY, LiY, LiJ, et al. (2013) Lyn regulates inflammatory responses in Klebsiella pneumoniae infection via the p38/NF-kappaB pathway. Eur J Immunol doi: 10.1002/eji.201343972
36. YangL, JelsbakL, MarvigRL, DamkiaerS, WorkmanCT, et al. (2011) Evolutionary dynamics of bacteria in a human host environment. Proc Natl Acad Sci U S A 108: 7481–7486.
37. WillettJW, KirbyJR (2012) Genetic and biochemical dissection of a HisKA domain identifies residues required exclusively for kinase and phosphatase activities. PLoS Genet 8: e1003084.
38. JeukensJ, BoyleB, BianconiI, Kukavica-IbruljI, TummlerB, et al. (2013) Complete Genome Sequence of Persistent Cystic Fibrosis Isolate Pseudomonas aeruginosa Strain RP73. Genome Announc 1: e00568–13.
39. AminM, PorterSL, SoyerOS (2013) Split histidine kinases enable ultrasensitivity and bistability in two-component signaling networks. PLoS Comput Biol 9: e1002949.
40. HuynhTN, StewartV (2011) Negative control in two-component signal transduction by transmitter phosphatase activity. Mol Microbiol 82: 275–286.
41. KenneyLJ (2010) How important is the phosphatase activity of sensor kinases? Curr Opin Microbiol 13: 168–176.
42. RaivioTL, SilhavyTJ (1997) Transduction of envelope stress in Escherichia coli by the Cpx two-component system. J Bacteriol 179: 7724–7733.
43. KostakiotiM, HadjifrangiskouM, PinknerJS, HultgrenSJ (2009) QseC-mediated dephosphorylation of QseB is required for expression of genes associated with virulence in uropathogenic Escherichia coli. Mol Microbiol 73: 1020–1031.
44. DengX, LanL, XiaoY, KennellyM, ZhouJM, et al. (2010) Pseudomonas syringae two-component response regulator RhpR regulates promoters carrying an inverted repeat element. Mol Plant Microbe Interact 23: 927–939.
45. XiaoY, LanL, YinC, DengX, BakerD, et al. (2007) Two-component sensor RhpS promotes induction of Pseudomonas syringae type III secretion system by repressing negative regulator RhpR. Mol Plant Microbe Interact 20: 223–234.
46. LimmerS, HallerS, DrenkardE, LeeJ, YuS, et al. (2011) Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model. Proc Natl Acad Sci U S A 108: 17378–17383.
47. RahmeLG, StevensEJ, WolfortSF, ShaoJ, TompkinsRG, et al. (1995) Common virulence factors for bacterial pathogenicity in plants and animals. Science 268: 1899–1902.
48. 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.
49. CostertonJW, StewartPS, GreenbergEP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284: 1318–1322.
50. SmithEE, BuckleyDG, WuZ, SaenphimmachakC, HoffmanLR, et al. (2006) Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci U S A 103: 8487–8492.
51. OliverA, CantonR, CampoP, BaqueroF, BlazquezJ (2000) High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288: 1251–1254.
52. DamkiaerS, YangL, MolinS, JelsbakL (2013) Evolutionary remodeling of global regulatory networks during long-term bacterial adaptation to human hosts. Proc Natl Acad Sci U S A 110: 7766–7771.
53. YangL, JelsbakL, MolinS (2011) Microbial ecology and adaptation in cystic fibrosis airways. Environ Microbiol 13: 1682–1689.
54. YangL, RauMH, YangL, HoibyN, MolinS, et al. (2011) Bacterial adaptation during chronic infection revealed by independent component analysis of transcriptomic data. BMC Microbiol 11: 184.
55. TralauT, VuilleumierS, ThibaultC, CampbellBJ, HartCA, et al. (2007) Transcriptomic analysis of the sulfate starvation response of Pseudomonas aeruginosa. J Bacteriol 189: 6743–6750.
56. JacobsMA, AlwoodA, ThaipisuttikulI, SpencerD, HaugenE, et al. (2003) Comprehensive transposon mutant library of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 100: 14339–14344.
57. BrintJM, OhmanDE (1995) Synthesis of multiple exoproducts in Pseudomonas aeruginosa is under the control of RhlR-RhlI, another set of regulators in strain PAO1 with homology to the autoinducer-responsive LuxR-LuxI family. J Bacteriol 177: 7155–7163.
58. SchweizerHP, HoangTT (1995) An improved system for gene replacement and xylE fusion analysis in Pseudomonas aeruginosa. Gene 158: 15–22.
59. BecherA, SchweizerHP (2000) Integration-proficient Pseudomonas aeruginosa vectors for isolation of single-copy chromosomal lacZ and lux gene fusions. Biotechniques 29: 948–950, 952.
60. JansonsI, TouchieG, SharpR, AlmquistK, FarinhaMA, et al. (1994) Deletion and transposon mutagenesis and sequence analysis of the pRO1600 OriR region found in the broad-host-range plasmids of the pQF series. Plasmid 31: 265–274.
61. LiuX, SunX, WuY, XieC, ZhangW, et al. (2013) Oxidation-sensing regulator AbfR regulates oxidative stress responses, bacterial aggregation, and biofilm formation in Staphylococcus epidermidis. J Biol Chem 288: 3739–3752.
62. SunF, DingY, JiQ, LiangZ, DengX, et al. (2012) Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance. Proc Natl Acad Sci U S A 109: 15461–15466.
63. DuanK, DammelC, SteinJ, RabinH, SuretteMG (2003) Modulation of Pseudomonas aeruginosa gene expression by host microflora through interspecies communication. Mol Microbiol 50: 1477–1491.
64. DuanK, SuretteMG (2007) Environmental regulation of Pseudomonas aeruginosa PAO1 Las and Rhl quorum-sensing systems. J Bacteriol 189: 4827–4836.
65. LanL, ChenW, LaiY, SuoJ, KongZ, et al. (2004) Monitoring of gene expression profiles and isolation of candidate genes involved in pollination and fertilization in rice (Oryza sativa L.) with a 10K cDNA microarray. Plant Mol Biol 54: 471–487.
66. LivakKJ, SchmittgenTD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402–408.
67. BarbieriCM, StockAM (2008) Universally applicable methods for monitoring response regulator aspartate phosphorylation both in vitro and in vivo using Phos-tag-based reagents. Anal Biochem 376: 73–82.
68. LiangH, DengX, JiQ, SunF, ShenT, et al. (2012) The Pseudomonas aeruginosa global regulator VqsR directly inhibits QscR to control quorum-sensing and virulence gene expression. J Bacteriol 194: 3098–3108.
69. KohlerT, van DeldenC, CurtyLK, HamzehpourMM, PechereJC (2001) Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell signaling in Pseudomonas aeruginosa. J Bacteriol 183: 5213–5222.
70. ZianniM, TessanneK, MerighiM, LagunaR, TabitaFR (2006) Identification of the DNA bases of a DNase I footprint by the use of dye primer sequencing on an automated capillary DNA analysis instrument. J Biomol Tech 17: 103–113.
71. IrizarryRA, HobbsB, CollinF, Beazer-BarclayYD, AntonellisKJ, et al. (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4: 249–264.
72. TusherVG, TibshiraniR, ChuG (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A 98: 5116–5121.
73. YuanK, HuangC, FoxJ, LaturnusD, CarlsonE, et al. (2012) Autophagy plays an essential role in the clearance of Pseudomonas aeruginosa by alveolar macrophages. J Cell Sci 125: 507–515.
74. KannanS, AudetA, KnittelJ, MullegamaS, GaoGF, et al. (2006) Src kinase Lyn is crucial for Pseudomonas aeruginosa internalization into lung cells. Eur J Immunol 36: 1739–1752.
75. WuM, HuangH, ZhangW, KannanS, WeaverA, et al. (2011) Host DNA repair proteins in response to Pseudomonas aeruginosa in lung epithelial cells and in mice. Infect Immun 79: 75–87.
76. WuM, BrownWL, StockleyPG (1995) Cell-specific delivery of bacteriophage-encapsidated ricin A chain. Bioconjug Chem 6: 587–595.
77. GoldovaJ, UlrychA, HercikK, BrannyP (2011) A eukaryotic-type signalling system of Pseudomonas aeruginosa contributes to oxidative stress resistance, intracellular survival and virulence. BMC Genomics 12: 437.
78. FiliatraultMJ, PicardoKF, NgaiH, PassadorL, IglewskiBH (2006) Identification of Pseudomonas aeruginosa genes involved in virulence and anaerobic growth. Infect Immun 74: 4237–4245.
79. RahmeLG, TanMW, LeL, WongSM, TompkinsRG, et al. (1997) Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors. Proc Natl Acad Sci U S A 94: 13245–13250.
80. SiehnelR, TraxlerB, AnDD, ParsekMR, SchaeferAL, et al. (2010) A unique regulator controls the activation threshold of quorum-regulated genes in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 107: 7916–7921.
81. WhiteleyM, ParsekMR, GreenbergEP (2000) Regulation of quorum sensing by RpoS in Pseudomonas aeruginosa. J Bacteriol 182: 4356–4360.
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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