RpoS Plays a Central Role in the SOS Induction by Sub-Lethal Aminoglycoside Concentrations in

English version České info

Bacteria encounter sub-inhibitory concentrations of antibiotics in various niches, where these low doses play a key role for antibiotic resistance selection. However, the physiological effects of these sub-lethal concentrations and their observed connection to the cellular mechanisms generating genetic diversification are still poorly understood. It is known that, unlike for the model bacterium Escherichia coli, sub-minimal inhibitory concentrations (sub-MIC) of aminoglycosides (AGs) induce the SOS response in Vibrio cholerae. SOS is induced upon DNA damage, and since AGs do not directly target DNA, we addressed two issues in this study: how sub-MIC AGs induce SOS in V. cholerae and why they do not do so in E. coli. We found that when bacteria are grown with tobramycin at a concentration 100-fold below the MIC, intracellular reactive oxygen species strongly increase in V. cholerae but not in E. coli. Using flow cytometry and gfp fusions with the SOS regulated promoter of intIA, we followed AG-dependent SOS induction. Testing the different mutation repair pathways, we found that over-expression of the base excision repair (BER) pathway protein MutY relieved this SOS induction in V. cholerae, suggesting a role for oxidized guanine in AG-mediated indirect DNA damage. As a corollary, we established that a BER pathway deficient E. coli strain induces SOS in response to sub-MIC AGs. We finally demonstrate that the RpoS general stress regulator prevents oxidative stress-mediated DNA damage formation in E. coli. We further show that AG-mediated SOS induction is conserved among the distantly related Gram negative pathogens Klebsiella pneumoniae and Photorhabdus luminescens, suggesting that E. coli is more of an exception than a paradigm for the physiological response to antibiotics sub-MIC.

Vyšlo v časopise: RpoS Plays a Central Role in the SOS Induction by Sub-Lethal Aminoglycoside Concentrations in. PLoS Genet 9(4): e32767. doi:10.1371/journal.pgen.1003421
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003421

Souhrn

Zdroje

1. BaharogluZ, BikardD, MazelD (2010) Conjugative DNA transfer induces the bacterial SOS response and promotes antibiotic resistance development through integron activation. PLoS Genet 6: e1001165 doi:10.1371/journal.pgen.1001165.

2. BaharogluZ, KrinE, MazelD (2012) Transformation-induced SOS regulation and carbon catabolite control of the V. cholerae integron integrase: connecting environment and genome plasticity. J Bacteriol

3. BaharogluZ, MazelD (2011) Vibrio cholerae triggers SOS and mutagenesis in response to a wide range of antibiotics, a route towards multi-resistance. Antimicrob Agents Chemother

4. WalkerGC (1996) The SOS Response of Escherichia coli. Escherichia coli and Salmonella. Neidhardt, FC Washington DC American Society of Microbiology 1: 1400–1416.

5. FickJ, SoderstromH, LindbergRH, PhanC, TysklindM, et al. (2009) Contamination of surface, ground, and drinking water from pharmaceutical production. Environ Toxicol Chem 28: 2522–2527.

6. HughesD, AnderssonDI (2012) Selection of resistance at lethal and non-lethal antibiotic concentrations. Curr Opin Microbiol 15: 555–560.

7. LiuYC, HuangWK, HuangTS, KuninCM (1999) Detection of antimicrobial activity in urine for epidemiologic studies of antibiotic use. J Clin Epidemiol 52: 539–545.

8. HaggardBE, BartschLD (2009) Net changes in antibiotic concentrations downstream from an effluent discharge. J Environ Qual 38: 343–352.

9. DaviesJ, SpiegelmanGB, YimG (2006) The world of subinhibitory antibiotic concentrations. Curr Opin Microbiol 9: 445–453.

10. KohanskiMA, DePristoMA, CollinsJJ (2010) Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis. Mol Cell 37: 311–320.

11. JenaNR (2012) DNA damage by reactive species: Mechanisms, mutation and repair. J Biosci 37: 503–517.

12. DalyMJ (2009) A new perspective on radiation resistance based on Deinococcus radiodurans. Nat Rev Microbiol 7: 237–245.

13. KeyerK, ImlayJA (1996) Superoxide accelerates DNA damage by elevating free-iron levels. Proc Natl Acad Sci U S A 93: 13635–13640.

14. TouatiD (2000) Iron and oxidative stress in bacteria. Arch Biochem Biophys 373: 1–6.

15. KuzminovA (1999) Recombinational repair of DNA damage in Escherichia coli and bacteriophage lambda. Microbiol Mol Biol Rev 63: 751–813, table of contents.

16. LuAL, LiX, GuY, WrightPM, ChangDY (2001) Repair of oxidative DNA damage: mechanisms and functions. Cell Biochem Biophys 35: 141–170.

17. SobolRW (2012) For MutY, it's all about the OG. Chem Biol 19: 313–314.

18. FotiJJ, DevadossB, WinklerJA, CollinsJJ, WalkerGC (2012) Oxidation of the guanine nucleotide pool underlies cell death by bactericidal antibiotics. Science 336: 315–319.

19. DukanS, FarewellA, BallesterosM, TaddeiF, RadmanM, et al. (2000) Protein oxidation in response to increased transcriptional or translational errors. Proc Natl Acad Sci U S A 97: 5746–5749.

20. Al MamunAA, GautamS, HumayunMZ (2006) Hypermutagenesis in mutA cells is mediated by mistranslational corruption of polymerase, and is accompanied by replication fork collapse. Mol Microbiol 62: 1752–1763.

21. KriskoA, RadmanM (2010) Protein damage and death by radiation in Escherichia coli and Deinococcus radiodurans. Proc Natl Acad Sci U S A 107: 14373–14377.

22. AllenKJ, GriffithsMW (2012) Impact of hydroxyl- and superoxide anion-based oxidative stress on logarithmic and stationary phase Escherichia coli O157:H7 stress and virulence gene expression. Food Microbiol 29: 141–147.

23. WeberH, PolenT, HeuvelingJ, WendischVF, HenggeR (2005) Genome-wide analysis of the general stress response network in Escherichia coli: sigmaS-dependent genes, promoters, and sigma factor selectivity. J Bacteriol 187: 1591–1603.

24. MerrikhH, FerrazzoliAE, BougdourA, Olivier-MasonA, LovettST (2009) A DNA damage response in Escherichia coli involving the alternative sigma factor, RpoS. Proc Natl Acad Sci U S A 106: 611–616.

25. MerrikhH, FerrazzoliAE, LovettST (2009) Growth phase and (p)ppGpp control of IraD, a regulator of RpoS stability, in Escherichia coli. J Bacteriol 191: 7436–7446.

26. BattestiA, TsegayeYM, PackerDG, MajdalaniN, GottesmanS (2012) H-NS Regulation of IraD and IraM Anti-adaptors for Control of RpoS Degradation. J Bacteriol

27. BarthE, GoraKV, GebendorferKM, SetteleF, JakobU, et al. (2009) Interplay of cellular cAMP levels, {sigma}S activity and oxidative stress resistance in Escherichia coli. Microbiology 155: 1680–1689.

28. HenleES, LinnS (1997) Formation, prevention, and repair of DNA damage by iron/hydrogen peroxide. J Biol Chem 272: 19095–19098.

29. ParkKJ, KangMJ, KimSH, LeeHJ, LimJK, et al. (2004) Isolation and characterization of rpoS from a pathogenic bacterium, Vibrio vulnificus: role of sigmaS in survival of exponential-phase cells under oxidative stress. J Bacteriol 186: 3304–3312.

30. Hengge-AronisR (2002) Signal transduction and regulatory mechanisms involved in control of the sigma(S) (RpoS) subunit of RNA polymerase. Microbiol Mol Biol Rev 66: 373–395, table of contents.

31. McCullenCA, BenhammouJN, MajdalaniN, GottesmanS (2010) Mechanism of positive regulation by DsrA and RprA small noncoding RNAs: pairing increases translation and protects rpoS mRNA from degradation. J Bacteriol 192: 5559–5571.

32. BougdourA, CunningC, BaptistePJ, ElliottT, GottesmanS (2008) Multiple pathways for regulation of sigmaS (RpoS) stability in Escherichia coli via the action of multiple anti-adaptors. Mol Microbiol 68: 298–313.

33. BougdourA, WicknerS, GottesmanS (2006) Modulating RssB activity: IraP, a novel regulator of sigma(S) stability in Escherichia coli. Genes Dev 20: 884–897.

34. WebbC, MorenoM, Wilmes-RiesenbergM, CurtissR3rd, FosterJW (1999) Effects of DksA and ClpP protease on sigma S production and virulence in Salmonella typhimurium. Mol Microbiol 34: 112–123.

35. WilhelmJ, VytasekR, OstadalovaI, VajnerL (2009) Evaluation of different methods detecting intracellular generation of free radicals. Mol Cell Biochem 328: 167–176.

36. HendersonLM, ChappellJB (1993) Dihydrorhodamine 123: a fluorescent probe for superoxide generation? Eur J Biochem 217: 973–980.

37. AuKG, ClarkS, MillerJH, ModrichP (1989) Escherichia coli mutY gene encodes an adenine glycosylase active on G-A mispairs. Proc Natl Acad Sci U S A 86: 8877–8881.

38. FloresMJ, SanchezN, MichelB (2005) A fork-clearing role for UvrD. Mol Microbiol 57: 1664–1675.

39. IgarashiK, KashiwagiK (2006) Polyamine Modulon in Escherichia coli: genes involved in the stimulation of cell growth by polyamines. J Biochem 139: 11–16.

40. JungIL, KimIG (2003) Transcription of ahpC, katG, and katE genes in Escherichia coli is regulated by polyamines: polyamine-deficient mutant sensitive to H2O2-induced oxidative damage. Biochem Biophys Res Commun 301: 915–922.

41. TkachenkoAG, AkhovaAV, ShumkovMS, NesterovaLY (2012) Polyamines reduce oxidative stress in Escherichia coli cells exposed to bactericidal antibiotics. Res Microbiol 163: 83–91.

42. HuangSH, ChenYH, KongG, ChenSH, BesemerJ, et al. (2001) A novel genetic island of meningitic Escherichia coli K1 containing the ibeA invasion gene (GimA): functional annotation and carbon-source-regulated invasion of human brain microvascular endothelial cells. Funct Integr Genomics 1: 312–322.

43. GuillemetML, MoreauPL (2008) Fur-dependent detoxification of organic acids by rpoS mutants during prolonged incubation under aerobic, phosphate starvation conditions. J Bacteriol 190: 5567–5575.

44. SikoraAE, BeyhanS, BagdasarianM, YildizFH, SandkvistM (2009) Cell envelope perturbation induces oxidative stress and changes in iron homeostasis in Vibrio cholerae. J Bacteriol 191: 5398–5408.

45. WholeyWY, JakobU (2012) Hsp33 confers bleach resistance by protecting elongation factor Tu against oxidative degradation in Vibrio cholerae. Mol Microbiol 83: 981–991.

46. MeyAR, WyckoffEE, KanukurthyV, FisherCR, PayneSM (2005) Iron and fur regulation in Vibrio cholerae and the role of fur in virulence. Infect Immun 73: 8167–8178.

47. MikaF, BusseS, PosslingA, BerkholzJ, TschowriN, et al. (2012) Targeting of csgD by the small regulatory RNA RprA links stationary phase, biofilm formation and cell envelope stress in Escherichia coli. Mol Microbiol

48. LaubacherME, AdesSE (2008) The Rcs phosphorelay is a cell envelope stress response activated by peptidoglycan stress and contributes to intrinsic antibiotic resistance. J Bacteriol 190: 2065–2074.

49. CalhounLN, KwonYM (2011) The ferritin-like protein Dps protects Salmonella enterica serotype Enteritidis from the Fenton-mediated killing mechanism of bactericidal antibiotics. Int J Antimicrob Agents 37: 261–265.

50. DongT, SchellhornHE (2010) Role of RpoS in virulence of pathogens. Infect Immun 78: 887–897.

51. Santos-ZavaletaA, Gama-CastroS, Perez-RuedaE (2011) A comparative genome analysis of the RpoS sigmulon shows a high diversity of responses and origins. Microbiology 157: 1393–1401.

52. LevertM, ZamfirO, ClermontO, BouvetO, LespinatsS, et al. (2010) Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections. PLoS Pathog 6: e1001125 doi:10.1371/journal.ppat.1001125.

53. RozenDE, PhilippeN, Arjan de VisserJ, LenskiRE, SchneiderD (2009) Death and cannibalism in a seasonal environment facilitate bacterial coexistence. Ecol Lett 12: 34–44.

54. MaL, ChenJ, LiuR, ZhangXH, JiangYA (2009) Mutation of rpoS gene decreased resistance to environmental stresses, synthesis of extracellular products and virulence of Vibrio anguillarum. FEMS Microbiol Ecol 70: 130–136.

55. MerrellDS, TischlerAD, LeeSH, CamilliA (2000) Vibrio cholerae requires rpoS for efficient intestinal colonization. Infect Immun 68: 6691–6696.

56. NielsenAT, DolganovNA, OttoG, MillerMC, WuCY, et al. (2006) RpoS controls the Vibrio cholerae mucosal escape response. PLoS Pathog 2: e109 doi:10.1371/journal.ppat.0020109.

57. ChiangSM, SchellhornHE (2010) Evolution of the RpoS regulon: origin of RpoS and the conservation of RpoS-dependent regulation in bacteria. J Mol Evol 70: 557–571.

58. MazelD, DychincoB, WebbVA, DaviesJ (1998) A distinctive class of integron in the Vibrio cholerae genome. Science 280: 605–608.

59. Rowe-MagnusDA, GueroutAM, BiskriL, BouigeP, MazelD (2003) Comparative analysis of superintegrons: engineering extensive genetic diversity in the Vibrionaceae. Genome Res 13: 428–442.

60. Rowe-MagnusDA, GueroutAM, PloncardP, DychincoB, DaviesJ, et al. (2001) The evolutionary history of chromosomal super-integrons provides an ancestry for multiresistant integrons. Proc Natl Acad Sci U S A 98: 652–657.

61. Rowe-MagnusDA, GueroutAM, MazelD (2002) Bacterial resistance evolution by recruitment of super-integron gene cassettes. Mol Microbiol 43: 1657–1669.

62. JoveT, Da ReS, DenisF, MazelD, PloyMC (2010) Inverse correlation between promoter strength and excision activity in class 1 integrons. PLoS Genet 6: e1000793 doi:10.1371/journal.pgen.1000793.

63. MazelD (2006) Integrons: agents of bacterial evolution. Nat Rev Microbiol 4: 608–620.

64. CambrayG, Sanchez-AlberolaN, CampoyS, GuerinE, Da ReS, et al. (2011) Prevalence of SOS-mediated control of integron integrase expression as an adaptive trait of chromosomal and mobile integrons. Mob DNA 2: 6.

65. GuerinE, CambrayG, Sanchez-AlberolaN, CampoyS, ErillI, et al. (2009) The SOS response controls integron recombination. Science 324: 1034.

66. PartridgeSR, TsafnatG, CoieraE, IredellJR (2009) Gene cassettes and cassette arrays in mobile resistance integrons. FEMS Microbiol Rev 33: 757–784.

67. HocquetD, LlanesC, ThouverezM, KulasekaraHD, BertrandX, et al. (2012) Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting. PLoS Pathog 8: e1002778 doi:10.1371/journal.ppat.1002778.

68. BennettHP, ClarkeDJ (2005) The pbgPE operon in Photorhabdus luminescens is required for pathogenicity and symbiosis. J Bacteriol 187: 77–84.

69. RuizN, SilhavyTJ (2003) Constitutive activation of the Escherichia coli Pho regulon upregulates rpoS translation in an Hfq-dependent fashion. J Bacteriol 185: 5984–5992.

70. CoynaultC, Robbe-SauleV, NorelF (1996) Virulence and vaccine potential of Salmonella typhimurium mutants deficient in the expression of the RpoS (sigma S) regulon. Mol Microbiol 22: 149–160.

71. TajiriT, MakiH, SekiguchiM (1995) Functional cooperation of MutT, MutM and MutY proteins in preventing mutations caused by spontaneous oxidation of guanine nucleotide in Escherichia coli. Mutat Res 336: 257–267.