Oxidative stress antagonizes fluoroquinolone drug sensitivity via the SoxR-SUF Fe-S cluster homeostatic axis


Autoři: Audrey Gerstel aff001;  Jordi Zamarreño Beas aff001;  Yohann Duverger aff001;  Emmanuelle Bouveret aff002;  Frédéric Barras aff001;  Béatrice Py aff001
Působiště autorů: Laboratoire de Chimie Bactérienne, Aix-Marseille Université-CNRS UMR7283, Institut de Microbiologie de la Méditerranée, Marseille, France aff001;  Laboratoire de Chimie Bactérienne, Institut de Microbiologie de la Méditerranée, Aix-Marseille Université, Marseille, France aff001;  SAMe Unit, Département de Microbiologie, Institut Pasteur, CNRS UMR IMM 2001, Paris, France aff002
Vyšlo v časopise: Oxidative stress antagonizes fluoroquinolone drug sensitivity via the SoxR-SUF Fe-S cluster homeostatic axis. PLoS Genet 16(11): e1009198. doi:10.1371/journal.pgen.1009198
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009198

Souhrn

The level of antibiotic resistance exhibited by bacteria can vary as a function of environmental conditions. Here, we report that phenazine-methosulfate (PMS), a redox-cycling compound (RCC) enhances resistance to fluoroquinolone (FQ) norfloxacin. Genetic analysis showed that E. coli adapts to PMS stress by making Fe-S clusters with the SUF machinery instead of the ISC one. Based upon phenotypic analysis of soxR, acrA, and micF mutants, we showed that PMS antagonizes fluoroquinolone toxicity by SoxR-mediated up-regulation of the AcrAB drug efflux pump. Subsequently, we showed that despite the fact that SoxR could receive its cluster from either ISC or SUF, only SUF is able to sustain efficient SoxR maturation under exposure to prolonged PMS period or high PMS concentrations. This study furthers the idea that Fe-S cluster homeostasis acts as a sensor of environmental conditions, and because its broad influence on cell metabolism, modifies the antibiotic resistance profile of E. coli.

Klíčová slova:

Antibiotic resistance – Antibiotics – Biosynthesis – DNA transcription – Homeostasis – Operons – Oxidative stress – Plasmid construction


Zdroje

1. Levy SB, Marshall B. Antibacterial resistance worldwide: causes, challenges and responses. Nat Med. 2004;10:S122–129. doi: 10.1038/nm1145 15577930

2. Chait R, Craney A, Kishony R. Antibiotic interactions that select against resistance. Nature. 2007;446:668–671. doi: 10.1038/nature05685 17410176

3. Yeh P, Tschumi AI, Kishony R. Functional classification of drugs by properties of their pairwise interactions. Nat Genet. 2006;38:489–494. doi: 10.1038/ng1755 16550172

4. Chevereau G, Bollenbach T. Systematic discovery of drug interaction mechanisms. Mol Syst Biol. 2015;11:807. doi: 10.15252/msb.20156098 25924924

5. Brochado AR, Telzerow A, Bobonis J, Banzhaf M, Mateus A, Selkrig J, et al. Species-specific activity of antibacterial drug combinations. Nature. 2018; 1. doi: 10.1038/s41586-018-0278-9 29973719

6. Burger RM, Drlica K. Superoxide protects Escherichia coli from bleomycin mediated lethality. J Inorg Biochem. 2009;103:1273–1277. doi: 10.1016/j.jinorgbio.2009.07.009 19679357

7. Mosel M, Li L, Drlica K, Zhao X. Superoxide-mediated protection of Escherichia coli from antimicrobials. Antimicrob Agents Chemother. 2013;57:5755–5759. doi: 10.1128/AAC.00754-13 23979754

8. Ezraty B, Vergnes A, Banzhaf M, Duverger Y, Huguenot A, Brochado AR, et al. Fe-S cluster biosynthesis controls uptake of aminoglycosides in a ROS-less death pathway. Science. 2013;340:1583–1587. doi: 10.1126/science.1238328 23812717

9. Roche B, Aussel L, Ezraty B, Mandin P, Py B, Barras F. Iron/sulfur proteins biogenesis in prokaryotes: formation, regulation and diversity. Biochim Biophys Acta. 2013;1827:455–469. doi: 10.1016/j.bbabio.2012.12.010 23298813

10. Boyd ES, Thomas KM, Dai Y, Boyd JM, Outten FW. Interplay between oxygen and Fe-S cluster biogenesis: insights from the Suf pathway. Biochemistry. 2014;53:5834–5847. doi: 10.1021/bi500488r 25153801

11. Blanc B, Gerez C, Ollagnier de Choudens S. Assembly of Fe/S proteins in bacterial systems: Biochemistry of the bacterial ISC system. Biochim Biophys Acta. 2015;1853:1436–1447. doi: 10.1016/j.bbamcr.2014.12.009 25510311

12. Blanc B, Clémancey M, Latour J-M, Fontecave M, Ollagnier de Choudens S. Molecular investigation of iron-sulfur cluster assembly scaffolds under stress. Biochemistry. 2014;53:7867–7869. doi: 10.1021/bi5012496 25485887

13. Bai Y, Chen T, Happe T, Lu Y, Sawyer A. Iron-sulphur cluster biogenesis via the SUF pathway. Metallomics. 2018;10:1038–1052. doi: 10.1039/c8mt00150b 30019043

14. Pérard J, Ollagnier de Choudens S. Iron-sulfur clusters biogenesis by the SUF machinery: close to the molecular mechanism understanding. J Biol Inorg Chem. 2018;23:581–596. doi: 10.1007/s00775-017-1527-3 29280002

15. Takahashi Y, Tokumoto U. A third bacterial system for the assembly of iron-sulfur clusters with homologs in archaea and plastids. J Biol Chem. 2002;277:28380–28383. doi: 10.1074/jbc.C200365200 12089140

16. Mettert EL, Kiley PJ. Fe–S proteins that regulate gene expression. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research. 2015;1853:1284–1293. doi: 10.1016/j.bbamcr.2014.11.018 25450978

17. Kobayashi K. Sensing Mechanisms in the Redox-Regulated, [2Fe-2S] Cluster-Containing, Bacterial Transcriptional Factor SoxR. Acc Chem Res. 2017;50:1672–1678. doi: 10.1021/acs.accounts.7b00137 28636310

18. Imlay JA. Transcription Factors That Defend Bacteria Against Reactive Oxygen Species. Annu Rev Microbiol. 2015;69:93–108. doi: 10.1146/annurev-micro-091014-104322 26070785

19. Dietrich LEP, Kiley PJ. A shared mechanism of SoxR activation by redox-cycling compounds. Mol Microbiol. 2011;79:1119–1122. doi: 10.1111/j.1365-2958.2011.07552.x 21338412

20. Pomposiello PJ, Bennik MH, Demple B. Genome-wide transcriptional profiling of the Escherichia coli responses to superoxide stress and sodium salicylate. J Bacteriol. 2001;183:3890–3902. doi: 10.1128/JB.183.13.3890-3902.2001 11395452

21. Martin RG, Rosner JL. Genomics of the marA/soxS/rob regulon of Escherichia coli: identification of directly activated promoters by application of molecular genetics and informatics to microarray data. Mol Microbiol. 2002;44:1611–1624. doi: 10.1046/j.1365-2958.2002.02985.x 12067348

22. Martin RG, Rosner JL. Analysis of microarray data for the marA, soxS, and rob regulons of Escherichia coli. Meth Enzymol. 2003;370:278–280. doi: 10.1016/S0076-6879(03)70024-X

23. Lee J- H, Lee K- L, Yeo W- S, Park S- J, Roe J- H. SoxRS-mediated lipopolysaccharide modification enhances resistance against multiple drugs in Escherichia coli. J Bacteriol. 2009;191:4441–4450. doi: 10.1128/JB.01474-08 19376854

24. Singh AK, Shin J- H, Lee K- L, Imlay JA, Roe J- H. Comparative study of SoxR activation by redox-active compounds. Mol Microbiol. 2013;90:983–996. doi: 10.1111/mmi.12410 24112649

25. Gaudu P, Weiss B. SoxR, a [2Fe-2S] transcription factor, is active only in its oxidized form. Proc Natl Acad Sci USA. 1996;93:10094–10098. doi: 10.1073/pnas.93.19.10094 8816757

26. Hidalgo E, Ding H, Demple B. Redox signal transduction: mutations shifting [2Fe-2S] centers of the SoxR sensor-regulator to the oxidized form. Cell. 1997;88:121–129. doi: 10.1016/s0092-8674(00)81864-4 9019397

27. Andersen J, Forst SA, Zhao K, Inouye M, Delihas N. The function of micF RNA. micF RNA is a major factor in the thermal regulation of OmpF protein in Escherichia coli. J Biol Chem. 1989;264:17961–17970. 2478539

28. Ma D, Cook DN, Alberti M, Pon NG, Nikaido H, Hearst JE. Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol Microbiol. 1995;16:45–55. doi: 10.1111/j.1365-2958.1995.tb02390.x 7651136

29. Okusu H, Ma D, Nikaido H. AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants. J Bacteriol. 1996;178:306–308. doi: 10.1128/jb.178.1.306-308.1996 8550435

30. Lee J-H, Yeo W-S, Roe J-H. Induction of the sufA operon encoding Fe-S assembly proteins by superoxide generators and hydrogen peroxide: involvement of OxyR, IHF and an unidentified oxidant-responsive factor. Mol Microbiol. 2004;51:1745–1755. doi: 10.1111/j.1365-2958.2003.03946.x 15009899

31. Yeo W-S, Lee J-H, Lee K-C, Roe J-H. IscR acts as an activator in response to oxidative stress for the suf operon encoding Fe-S assembly proteins. Mol Microbiol. 2006;61:206–218. doi: 10.1111/j.1365-2958.2006.05220.x 16824106

32. Hassan HM, Fridovich I. Intracellular production of superoxide radical and of hydrogen peroxide by redox active compounds. Arch Biochem Biophys. 1979;196:385–395. doi: 10.1016/0003-9861(79)90289-3 225995

33. Ezraty B, Henry C, Hérisse M, Denamur E, Barras F. Commercial Lysogeny Broth culture media and oxidative stress: a cautious tale. Free Radic Biol Med. 2014;74:245–251. doi: 10.1016/j.freeradbiomed.2014.07.010 25048972

34. Koo M- S, Lee J- H, Rah S- Y, Yeo W- S, Lee J- W, Lee K- L, et al. A reducing system of the superoxide sensor SoxR in Escherichia coli. EMBO J. 2003;22:2614–2622. doi: 10.1093/emboj/cdg252 12773378

35. Vinella D, Loiseau L, Ollagnier de Choudens S, Fontecave M, Barras F. In vivo [Fe-S] cluster acquisition by IscR and NsrR, two stress regulators in Escherichia coli. Mol Microbiol. 2013;87:493–508. doi: 10.1111/mmi.12135 23320508

36. Vinella D, Brochier-Armanet C, Loiseau L, Talla E, Barras F. Iron-sulfur (Fe/S) protein biogenesis: phylogenomic and genetic studies of A-type carriers. PLoS Genet. 2009;5:e1000497. doi: 10.1371/journal.pgen.1000497 19478995

37. Py B, Gerez C, Huguenot A, Vidaud C, Fontecave M, Ollagnier de Choudens S, et al. The ErpA/NfuA complex builds an oxidation-resistant Fe-S cluster delivery pathway. J Biol Chem. 2018;293:7689–7702. doi: 10.1074/jbc.RA118.002160 29626095

38. Loiseau L, Gerez C, Bekker M, Ollagnier-de Choudens S, Py B, Sanakis Y, et al. ErpA, an iron sulfur (Fe S) protein of the A-type essential for respiratory metabolism in Escherichia coli. Proc Natl Acad Sci USA. 2007;104:13626–13631. doi: 10.1073/pnas.0705829104 17698959

39. Angelini S, Gerez C, Ollagnier-de Choudens S, Sanakis Y, Fontecave M, Barras F, et al. NfuA, a new factor required for maturing Fe/S proteins in Escherichia coli under oxidative stress and iron starvation conditions. J Biol Chem. 2008;283:14084–14091. doi: 10.1074/jbc.M709405200 18339628

40. Larson MH, Gilbert LA, Wang X, Lim WA, Weissman JS, Qi LS. CRISPR interference (CRISPRi) for sequence-specific control of gene expression. Nat Protoc. 2013;8:2180–2196. doi: 10.1038/nprot.2013.132 24136345

41. Chareyre S, Barras F, Mandin P. A small RNA controls bacterial sensitivity to gentamicin during iron starvation. PLoS Genet. 2019;15:e1008078. doi: 10.1371/journal.pgen.1008078 31009454

42. Crack JC, Le Brun NE. Redox-Sensing Iron-Sulfur Cluster Regulators. Antioxid Redox Signal. 2018;29:1809–1829. doi: 10.1089/ars.2017.7361 28967283

43. Mettert EL, Outten FW, Wanta B, Kiley PJ. The impact of O(2) on the Fe-S cluster biogenesis requirements of Escherichia coli FNR. J Mol Biol. 2008;384:798–811. doi: 10.1016/j.jmb.2008.09.080 18938178

44. Nachin L, Loiseau L, Expert D, Barras F. SufC: an unorthodox cytoplasmic ABC/ATPase required for [Fe-S] biogenesis under oxidative stress. EMBO J. 2003;22:427–437. doi: 10.1093/emboj/cdg061 12554644

45. Jang S, Imlay JA. Hydrogen peroxide inactivates the Escherichia coli Isc iron-sulphur assembly system, and OxyR induces the Suf system to compensate. Mol Microbiol. 2010;78:1448–1467. doi: 10.1111/j.1365-2958.2010.07418.x 21143317

46. Lee K- C, Yeo W- S, Roe J- H. Oxidant-responsive induction of the suf operon, encoding a Fe-S assembly system, through Fur and IscR in Escherichia coli. J Bacteriol. 2008;190:8244–8247. doi: 10.1128/JB.01161-08 18849427

47. Bentley SD, Chater KF, Cerdeño-Tárraga A- M, Challis GL, Thomson NR, James KD, et al. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature. 2002;417:141–147. doi: 10.1038/417141a 12000953

48. den Hengst CD, Buttner MJ. Redox control in actinobacteria. Biochim Biophys Acta. 2008;1780:1201–1216. doi: 10.1016/j.bbagen.2008.01.008 18252205

49. Pinske C, Sawers RG. Delivery of iron-sulfur clusters to the hydrogen-oxidizing [NiFe]-hydrogenases in Escherichia coli requires the A-type carrier proteins ErpA and IscA. PLoS ONE. 2012;7:e31755. doi: 10.1371/journal.pone.0031755 22363723

50. Pinske C, Sawers RG. A-type carrier protein ErpA is essential for formation of an active formate-nitrate respiratory pathway in Escherichia coli K-12. J Bacteriol. 2012;194:346–353. doi: 10.1128/JB.06024-11 22081393

51. Jaroschinsky M, Pinske C, Gary Sawers R. Differential effects of isc operon mutations on the biosynthesis and activity of key anaerobic metalloenzymes in Escherichia coli. Microbiology (Reading, Engl). 2017;163:878–890. doi: 10.1099/mic.0.000481 28640740

52. Tanaka N, Kanazawa M, Tonosaki K, Yokoyama N, Kuzuyama T, Takahashi Y. Novel features of the ISC machinery revealed by characterization of Escherichia coli mutants that survive without iron-sulfur clusters. Mol Microbiol. 2016;99:835–848. doi: 10.1111/mmi.13271 26560204

53. Mühlenhoff U, Richter N, Pines O, Pierik AJ, Lill R. Specialized function of yeast Isa1 and Isa2 proteins in the maturation of mitochondrial [4Fe-4S] proteins. J Biol Chem. 2017;292:17979. doi: 10.1074/jbc.AAC117.000255 29079644

54. Schwartz CJ, Djaman O, Imlay JA, Kiley PJ. The cysteine desulfurase, IscS, has a major role in in vivo Fe-S cluster formation in Escherichia coli. Proc Natl Acad Sci USA. 2000;97:9009–9014. doi: 10.1073/pnas.160261497 10908675

55. Sekiya H, Mima T, Morita Y, Kuroda T, Mizushima T, Tsuchiya T. Functional cloning and characterization of a multidrug efflux pump, mexHI-opmD, from a Pseudomonas aeruginosa mutant. Antimicrob Agents Chemother. 2003;47:2990–2992. doi: 10.1128/aac.47.9.2990-2992.2003 12937010

56. Palma M, Zurita J, Ferreras JA, Worgall S, Larone DH, Shi L, et al. Pseudomonas aeruginosa SoxR does not conform to the archetypal paradigm for SoxR-dependent regulation of the bacterial oxidative stress adaptive response. Infect Immun. 2005;73:2958–2966. doi: 10.1128/IAI.73.5.2958-2966.2005 15845502

57. Dietrich LEP, Price-Whelan A, Petersen A, Whiteley M, Newman DK. The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa. Mol Microbiol. 2006;61:1308–1321. doi: 10.1111/j.1365-2958.2006.05306.x 16879411

58. Sakhtah H, Koyama L, Zhang Y, Morales DK, Fields BL, Price-Whelan A, et al. The Pseudomonas aeruginosa efflux pump MexGHI-OpmD transports a natural phenazine that controls gene expression and biofilm development. PNAS. 2016; 201600424. doi: 10.1073/pnas.1600424113 27274079

59. Zhu K, Chen S, Sysoeva TA, You L. Universal antibiotic tolerance arising from antibiotic-triggered accumulation of pyocyanin in Pseudomonas aeruginosa. PLoS Biol. 2019;17:e3000573. doi: 10.1371/journal.pbio.3000573 31841520

60. Schiessl KT, Hu F, Jo J, Nazia SZ, Wang B, Price-Whelan A, et al. Phenazine production promotes antibiotic tolerance and metabolic heterogeneity in Pseudomonas aeruginosa biofilms. Nat Commun. 2019;10:762. doi: 10.1038/s41467-019-08733-w 30770834

61. Brynildsen MP, Winkler JA, Spina CS, MacDonald IC, Collins JJ. Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production. Nat Biotechnol. 2013;31:160–165. doi: 10.1038/nbt.2458 23292609

62. Miller JH. A Short Course in Bacterial Genetics–A Laboratory Manual and Handbook for Escherichia coli and Related Bacteria. Cold Spring Harbor 1992. Cold Spring Harbor Laboratory Press. ISBN: 0–87969–349–5.


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