Two-Component System Cross-Regulation Integrates Response to Heme and Cell Envelope Stress

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The vertebrate host is a hostile environment to microbes, where large variations in temperature, oxygen, and nutrient availability challenge microbial replication. In order to successfully infect vertebrates, pathogens must sense that they have entered their host and alter gene expression accordingly. One way bacteria adapt to their environment is by using two-component signaling systems (TCS), which are comprised of a signal sensor and a transcriptional regulator. The core signaling components of TCSs are conserved across the bacterial Kingdom; however, examples of interactions between two distinct TCS are extremely rare. Here we have probed how Bacillus anthracis, the causative agent of anthrax, adapts to life in the vertebrate host. The B. anthracis heme sensing TCS, HssRS, senses heme as a component of vertebrate blood and protects the bacteria from heme toxicity. We have identified a new TCS (HitRS), which is activated by compounds that alter the integrity of the cell envelope, and interacts with HssRS to coordinate a simultaneous response to both heme and cell envelope stress. This reciprocal HssRS-HitRS signaling is an unusual demonstration of bacterial signal cross-regulation and suggests that coordinating the response to heme and cell envelope stress is important for B. anthracis adaptation to the vertebrate host.

Vyšlo v časopise: Two-Component System Cross-Regulation Integrates Response to Heme and Cell Envelope Stress. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004044
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004044

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Zdroje

1. StockAM, RobinsonVL, GoudreauPN (2000) Two-component signal transduction. Annu Rev Biochem 69 : 183–215.

2. SkerkerJM, PerchukBS, SiryapornA, LubinEA, AshenbergO, et al. (2008) Rewiring the specificity of two-component signal transduction systems. Cell 133 : 1043–1054.

3. LaubMT, GoulianM (2007) Specificity in two-component signal transduction pathways. Annu Rev Genet 41 : 121–145.

4. PodgornaiaAI, LaubMT (2013) Determinants of specificity in two-component signal transduction. Curr Opin Microbiol 16 : 156–162.

5. SkerkerJM, PrasolMS, PerchukBS, BiondiEG, LaubMT (2005) Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: A system-level analysis. PLoS Biol 3: e334.

6. GrobanES, ClarkeEJ, SalisHM, MillerSM, VoigtCA (2009) Kinetic buffering of cross talk between bacterial two-component sensors. Journal of Molecular Biology 390 : 380–393.

7. CaiSJ, InouyeM (2002) EnvZ-OmpR interaction and osmoregulation in Escherichia coli. J Biol Chem 277 : 24155–24161.

8. 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.

9. FisherSL, JiangW, WannerBL, WalshCT (1995) Cross-talk between the histidine protein kinase VanS and the response regulator PhoB: Characterization and identification of a VanS domain that inhibits activation of PhoB. J Biol Chem 270 : 23143–23149.

10. SilvaJC, HaldimannA, PrahaladMK, WalshCT, WannerBL (1998) In vivo characterization of the type A and B vancomycin-resistant enterococci (VRE) VanRS two-component systems in Escherichia coli: a nonpathogenic model for studying the VRE signal transduction pathways. Proc Natl Acad Sci U S A 95 : 11951–11956.

11. SiryapornA, GoulianM (2008) Cross-talk suppression between the CpxA-CpxR and EnvZ-OmpR two-component systems in E. coli. Mol Microbiol 70 : 494–506.

12. SiryapornA, PerchukBS, LaubMT, GoulianM (2010) Evolving a robust signal transduction pathway from weak cross-talk. Mol Syst Biol 6 : 452.

13. MatsubaraM, KitaokaSI, TakedaSI, MizunoT (2000) Tuning of the porin expression under anaerobic growth conditions by His-to-Asp cross-phosphorelay through both the EnvZ-osmosensor and ArcB-anaerosensor in Escherichia coli. Genes Cells 5 : 555–569.

14. StewartV (2003) Biochemical Society Special Lecture. Nitrate -⁠ and nitrite-responsive sensors NarX and NarQ of proteobacteria. Biochem Soc Trans 31 : 1–10.

15. HowellA, DubracS, NooneD, VarugheseKI, DevineK (2006) Interactions between the YycFG and PhoPR two-component systems in Bacillus subtilis: the PhoR kinase phosphorylates the non-cognate YycF response regulator upon phosphate limitation. Mol Microbiol 59 : 1199–1215.

16. GuckesKR, KostakiotiM, BrelandEJ, GuAP, ShafferCL, et al. (2013) Strong cross-system interactions drive the activation of the QseB response regulator in the absence of its cognate sensor. Proc Natl Acad Sci U S A 110 : 16592–16597.

17. RietkotterE, HoyerD, MascherT (2008) Bacitracin sensing in Bacillus subtilis. Mol Microbiol 68 : 768–785.

18. GoodmanAL, MerighiM, HyodoM, VentreI, FillouxA, et al. (2009) Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen. Genes Dev 23 : 249–259.

19. JubelinG, VianneyA, BeloinC, GhigoJM, LazzaroniJC, et al. (2005) CpxR/OmpR interplay regulates curli gene expression in response to osmolarity in Escherichia coli. J Bacteriol 187 : 2038–2049.

20. BatchelorE, WalthersD, KenneyLJ, GoulianM (2005) The Escherichia coli CpxA-CpxR envelope stress response system regulates expression of the porins ompF and ompC. J Bacteriol 187 : 5723–5731.

21. DelgadoMA, MouslimC, GroismanEA (2006) The PmrA/PmrB and RcsC/YojN/RcsB systems control expression of the Salmonella O-antigen chain length determinant. Mol Microbiol 60 : 39–50.

22. MouslimC, GroismanEA (2003) Control of the Salmonella ugd gene by three two-component regulatory systems. Mol Microbiol 47 : 335–344.

23. DarwinAJ, TysonKL, BusbySJ, StewartV (1997) Differential regulation by the homologous response regulators NarL and NarP of Escherichia coli K-12 depends on DNA binding site arrangement. Mol Microbiol 25 : 583–595.

24. GunnJS, MillerSI (1996) PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance. J Bacteriol 178 : 6857–6864.

25. VianneyA, JubelinG, RenaultS, DorelC, LejeuneP, et al. (2005) Escherichia coli tol and rcs genes participate in the complex network affecting curli synthesis. Microbiology 151 : 2487–2497.

26. BirkeySM, LiuW, ZhangX, DugganMF, HulettFM (1998) Pho signal transduction network reveals direct transcriptional regulation of one two-component system by another two-component regulator: Bacillus subtilis PhoP directly regulates production of ResD. Mol Microbiol 30 : 943–953.

27. TonelloF, ZornettaI (2012) Bacillus anthracis factors for phagosomal escape. Toxins 4 : 536–553.

28. HonsaES, MaressoAW (2011) Mechanisms of iron import in anthrax. Biometals 24 : 533–545.

29. StauffDL, SkaarEP (2009) Bacillus anthracis HssRS signalling to HrtAB regulates haem resistance during infection. Molecular Microbiology 72 : 763–778.

30. LechardeurD, CesselinB, LieblU, VosMH, FernandezA, et al. (2012) Discovery of intracellular heme-binding protein HrtR, which controls heme efflux by the conserved HrtB-HrtA transporter in Lactococcus lactis. J Biol Chem 287 : 4752–4758.

31. 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.

32. MikeLA, DutterBF, StauffDL, MooreJL, VitkoNP, et al. (2013) Activation of heme biosynthesis by a small molecule that is toxic to fermenting Staphylococcus aureus. Proc Natl Acad Sci U S A 110 : 8206–8211.

33. de BeenM, BartMJ, AbeeT, SiezenRJ, FranckeC (2008) The identification of response regulator-specific binding sites reveals new roles of two-component systems in Bacillus cereus and closely related low-GC Gram-positives. Environ Microbiol 10 : 2796–2809.

34. LuJM, NurkoJ, WeakleySM, JiangJ, KougiasP, et al. (2010) Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: an update. Med Sci Monit 16: RA93–100.

35. DruckerAM, RosenCF (2011) Drug-induced photosensitivity. Drug Safety 34 : 821–837.

36. KlubesP, FayPJ, CernaI (1971) Effects of chlorpromazine on cell wall biosynthesis and incorporation of orotic acid into nucleic acids in Bacillus megaterium. Biochemical Pharmacology 20 : 265–277.

37. OrdalGW (1976) Recognition sites for chemotactic repellents of Bacillus subtilis. J Bacteriol 126 : 72–79.

38. Watanakunakorn C (1984) Mode of action and in-vitro activity of vancomycin. J Antimicrob Chemother 14 Suppl D: 7–18.

39. SwobodaJG, MeredithTC, CampbellJ, BrownS, SuzukiT, et al. (2009) Discovery of a small molecule that blocks wall teichoic acid biosynthesis in Staphylococcus aureus. ACS Chem Biol 4 : 875–883.

40. CampbellJ, SinghAK, SwobodaJG, GilmoreMS, WilkinsonBJ, et al. (2012) An antibiotic that inhibits a late step in wall teichoic acid biosynthesis induces the cell wall stress stimulon in Staphylococcus aureus. Antimicrob Agents Chemother 56 : 1810–1820.

41. SchirnerK, StoneLK, WalkerS (2011) ABC transporters required for export of wall teichoic acids do not discriminate between different main chain polymers. ACS Chem Biol 6 : 407–412.

42. SkaarEP, HumayunM, BaeT, DeBordKL, SchneewindO (2004) Iron-source preference of Staphylococcus aureus infections. Science 305 : 1626–1628.

43. AnzaldiLL, SkaarEP (2010) Overcoming the heme paradox: Heme toxicity and tolerance in bacterial pathogens. Infect Immun 78 : 4977–4989.

44. Kirschner-ZilberI, RabizadehE, ShaklaiN (1982) The interaction of hemin and bilirubin with the human red cell membrane. Biochim Biophys Acta 690 : 10.

45. SchmittTH, FrezzattiWA, SchreierS (1993) Hemin-induced lipid membrane disorder and increased permeability: a molecular model for the mechanism of cell lysis. Archives of Biochemistry and Biophysics 307 : 96–103.

46. ChouA, FitchC (1981) Mechanism of hemolysis induced by ferriprotoporphyrin IX. Journal of Clinical Investigation 68 : 6.

47. HeyningenV (1948) Inhibition of aerobic sporing Bacilli by Haematin. Nature 162 : 114.

48. JiangM, ShaoW, PeregoM, HochJA (2000) Multiple histidine kinases regulate entry into stationary phase and sporulation in Bacillus subtilis. Mol Microbiol 38 : 535–542.

49. FujitaM, LosickR (2005) Evidence that entry into sporulation in Bacillus subtilis is governed by a gradual increase in the level and activity of the master regulator Spo0A. Genes Dev 19 : 2236–2244.

50. SterneM (1937) Avirulent anthrax vaccine. Onderstepoort J Vet Sci Animal Ind 21 : 41–43.

51. KimHS, ShermanD, JohnsonF, AronsonAI (2004) Characterization of a major Bacillus anthracis spore coat protein and its role in spore inactivation. J Bacteriol 186 : 2413–2417.

52. KernJW, SchneewindO (2008) BslA, a pXO1-encoded adhesin of Bacillus anthracis. Mol Microbiol 68 : 504–515.

53. SchneewindO, ModelP, FischettiVA (1992) Sorting of protein A to the staphylococcal cell wall. Cell 70 : 267–281.

54. HortonRM, CaiZL, HoSN, PeaseLR (1990) Gene splicing by overlap extension: tailor-made genes using the polymerase chain reaction. Biotechniques 8 : 528–535.

55. StauffDL, BagaleyD, TorresVJ, JoyceR, AndersonKL, et al. (2008) Staphylococcus aureus HrtA is an ATPase required for protection against heme toxicity and prevention of a transcriptional heme stress response. J Bacteriol 190 : 3588–3596.

56. StauffDL, TorresVJ, SkaarEP (2007) Signaling and DNA-binding activities of the Staphylococcus aureus HssR-HssS two-component system required for heme sensing. J Biol Chem 282 : 26111–26121.