Role of reactive oxygen species in antibiotic action and resistance

Current Opinion in Microbiology

Volumn 12, Issue 5, 2009, Pages 482-489

  Dwyer, Daniel J ^a   Kohanski, Michael A ^a,b   Collins, James J ^a,b  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANTIBIOTIC AGENT; METRONIDAZOLE; REACTIVE OXYGEN METABOLITE; RIFAMPICIN; TOBRAMYCIN;

ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ANTIMICROBIAL ACTIVITY; BACTERIAL INFECTION; CELL DEATH; DNA REPAIR; DRUG METABOLISM; HUMAN; MUTAGENESIS; NONHUMAN; PROTEIN FUNCTION; REVIEW; TREATMENT RESPONSE;

ANTI-BACTERIAL AGENTS; BACTERIAL INFECTIONS; DRUG RESISTANCE, MULTIPLE, BACTERIAL; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES;

BACTERIA (MICROORGANISMS);

EID: 70349816733     PISSN: 13695274     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mib.2009.06.018     Document Type: Review

References (68)

1. Walsh C. Where will new antibiotics come from?. Nat Rev Microbiol 1 (2003) 65-70
2. Wright G.D. The antibiotic resistome: the nexus of chemical and genetic diversity. Nat Rev Microbiol 5 (2007) 175-186
3. Alekshun M.N., and Levy S.B. Molecular mechanisms of antibacterial multidrug resistance. Cell 128 (2007) 1037-1050
4. Storz G., and Hengge-Aronis R. Bacterial Stress Responses (2000), ASM Press, Washington, DC
5. Foster P.L. Stress-induced mutagenesis in bacteria. Crit Rev Biochem Mol Biol 42 (2007) 373-397
6. Radman M. Phenomenology of an inducible mutagenic DNA repair pathway in Escherichia coli: SOS repair hypothesis. In: Prakash L., Sherman F., Miller M., Lawrence C., and Tabor H. (Eds). Molecular and Environmental Aspects of Mutagenesis (1974), Charles C. Thomas 128-142
7. Witkin E.M. Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bacteriol Rev 40 (1976) 869-907
8. Guisbert E., Yura T., Rhodius V.A., and Gross C.A. Convergence of molecular, modeling, and systems approaches for an understanding of the Escherichia coli heat shock response. Microbiol Mol Biol Rev 72 (2008) 545-554
9. Storz G., and Imlay J.A. Oxidative stress. Curr Opin Microbiol 2 (1999) 188-194
10. Kohanski M.A., Dwyer D.J., Hayete B., Lawrence C.A., and Collins J.J. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130 (2007) 797-810. This work reveals that treatment of Gram-positive and Gram-negative bacteria with bactericidal antibiotics induces the formation of hydroxyl radicals via a common mechanism that involves drug-induced changes in cellular metabolism, notably the tricarboxylic acid cycle.
11. Levin D.E., Hollstein M., Christman M.F., Schwiers E.A., and Ames B.N. A new Salmonella tester strain (TA102) with A X T base pairs at the site of mutation detects oxidative mutagens. Proc Natl Acad Sci U S A 79 (1982) 7445-7449
12. Farr S.B., D'Ari R., and Touati D. Oxygen-dependent mutagenesis in Escherichia coli lacking superoxide dismutase. Proc Natl Acad Sci U S A 83 (1986) 8268-8272
13. Sakai A., Nakanishi M., Yoshiyama K., and Maki H. Impact of reactive oxygen species on spontaneous mutagenesis in Escherichia coli. Genes Cells 11 (2006) 767-778
14. Imlay J.A. Cellular defenses against superoxide and hydrogen peroxide. Annu Rev Biochem 77 (2008) 755-776. A comprehensive review that details the mechanism of reactive oxygen species generation in bacteria, as well as the layers of protection employed by bacteria in their defense against these toxic molecules.
15. Korshunov S., and Imlay J.A. Detection and quantification of superoxide formed within the periplasm of Escherichia coli. J Bacteriol 188 (2006) 6326-6334
16. Seaver L.C., and Imlay J.A. Are respiratory enzymes the primary sources of intracellular hydrogen peroxide?. J Biol Chem 279 (2004) 48742-48750
17. Imlay J.A. Pathways of oxidative damage. Annu Rev Microbiol 57 (2003) 395-418
18. Imlay J.A., Chin S.M., and Linn S. Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science 240 (1988) 640-642
19. Liochev S.I., and Fridovich I. Superoxide and iron: partners in crime. IUBMB Life 48 (1999) 157-161
20. Kiley P.J., and Beinert H. The role of Fe-S proteins in sensing and regulation in bacteria. Curr Opin Microbiol 6 (2003) 181-185
21. 2+ at RGGG-containing DNA sequences correlates with enhanced oxidative cleavage at such sequences. Nucleic Acids Res 33 (2005) 497-510
22. Balasubramanian B., Pogozelski W.K., and Tullius T.D. DNA strand breaking by the hydroxyl radical is governed by the accessible surface areas of the hydrogen atoms of the DNA backbone. Proc Natl Acad Sci U S A 95 (1998) 9738-9743
23. 2+-mediated Fenton reactions has possible biological implications. J Biol Chem 274 (1999) 962-971
24. Dwyer D.J., Kohanski M.A., and Collins J.J. Networking opportunities for bacteria. Cell 135 (2008) 1153-1156
25. Dwyer D.J., Kohanski M.A., Hayete B., and Collins J.J. Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli. Mol Syst Biol 3 (2007) 91. This work describes the responses of E. coli to gyrase inhibition by a fluoroquinolone antibiotic and a peptide toxin, which include activation of the superoxide stress response, derepression of the iron uptake and utilization regulon, and increased iron-sulfur cluster synthesis. Ultimately, these physiological changes result in hydroxyl radical production, which is shown to contribute to cell death.
26. Drlica K., Malik M., Kerns R.J., and Zhao X. Quinolone-mediated bacterial death. Antimicrob Agents Chemother 52 (2008) 385-392
27. Pomposiello P.J., and Demple B. Redox-operated genetic switches: the SoxR and OxyR transcription factors. Trends Biotechnol 19 (2001) 109-114
28. Ayala-Castro C., Saini A., and Outten F.W. Fe-S cluster assembly pathways in bacteria. Microbiol Mol Biol Rev 72 (2008) 110-125
29. Braun V. Iron uptake by Escherichia coli. Front Biosci 8 (2003) s1409-s1421
30. Friedberg E.C., Walker G.C., Siede W., Wood R.D., Schultz R.A., and Ellenberger T. DNA Repair and Mutagenesis. edn 2 (2006), ASM Press, Washington, DC
31. Wang X., and Zhao X. Contribution of oxidative damage to antimicrobial lethality. Antimicrob Agents Chemother 53 (2009) 1395-1402
32. Kolodkin-Gal I., Sat B., Keshet A., and Engelberg-Kulka H. The communication factor EDF and the toxin-antitoxin module mazEF determine the mode of action of antibiotics. PLoS Biol 6 (2008) e319
33. Tamae C., Liu A., Kim K., Sitz D., Hong J., Becket E., Bui A., Solaimani P., Tran K.P., Yang H., et al. Determination of antibiotic hypersensitivity among 4,000 single-gene-knockout mutants of Escherichia coli. J Bacteriol 190 (2008) 5981-5988
34. Girgis H.S., Hottes A.K., and Tavazoie S. Genetic architecture of intrinsic antibiotic susceptibility. PLoS ONE 4 (2009) e5629. This work describes a transposon-based mutagenesis screen which identified individual genes and biochemical pathways, in a sub-MIC growth assay, that differentially contribute to the increased or decreased sensitivity of E. coli to a wide range of bactericidal and bacteriostatic antibiotics.
35. Schurek K.N., Marr A.K., Taylor P.K., Wiegand I., Semenec L., Khaira B.K., and Hancock R.E. Novel genetic determinants of low-level aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 52 (2008) 4213-4219. This work describes the screening of a P. aeruginosa transposon mutant library for genes that individually increased the resistance of the bacterium to a clinically relevant aminoglycoside (tobramycin), defines a minimal resistome based on functional enrichment, and discusses the role of lipopolysaccharide synthesis mutants in decreased drug uptake.
36. Kohanski M.A., Dwyer D.J., Wierzbowski J., Cottarel G., and Collins J.J. Mistranslation of membrane proteins and two-component system activation trigger antibiotic-mediated cell death. Cell 135 (2008) 679-690
37. Cirz R.T., and Romesberg F.E. Controlling mutation: intervening in evolution as a therapeutic strategy. Crit Rev Biochem Mol Biol 42 (2007) 341-354
38. Cirz R.T., Chin J.K., Andes D.R., de Crecy-Lagard V., Craig W.A., and Romesberg F.E. Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biol 3 (2005) e176. This paper demonstrates that blocking the activation of the SOS response (by using an uncleavable LexA repressor mutant strain of E. coli), following treatment of E. coli-infected mice with either a fluoroquinolone or a rifamycin antibiotic, inhibits the evolution of resistance-conferring mutations. Additionally discusses the role of SOS component polymerases (i.e. pol V) in induced DNA mutagenesis in resistance formation.
39. Smith P.A., and Romesberg F.E. Combating bacteria and drug resistance by inhibiting mechanisms of persistence and adaptation. Nat Chem Biol 3 (2007) 549-556. A thought-provoking review covering resistance-forming mechanisms, including stress-induced mutagenesis and horizontal transfer of resistance-conferring genes, as well as the clinically relevant phenomenon of persistence. Also discusses ideas for exploiting these topics as antibacterial therapies.
40. Lu T.K., and Collins J.J. Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy. Proc Natl Acad Sci U S A 106 (2009) 4629-4634
41. Ysern P., Clerch B., Castano M., Gibert I., Barbe J., and Llagostera M. Induction of SOS genes in Escherichia coli and mutagenesis in Salmonella typhimurium by fluoroquinolones. Mutagenesis 5 (1990) 63-66
42. Drlica K., and Malik M. Fluoroquinolones: action and resistance. Curr Top Med Chem 3 (2003) 249-282
43. Beaber J.W., Hochhut B., and Waldor M.K. SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature 427 (2004) 72-74
44. Mesak L.R., Miao V., and Davies J. Effects of subinhibitory concentrations of antibiotics on SOS and DNA repair gene expression in Staphylococcus aureus. Antimicrob Agents Chemother 52 (2008) 3394-3397. This paper describes the screening of several clinically derived strains and laboratory strains of S. aureus (including several resistants to the fluoroquinolone, ciprofloxacin), with sub-MIC levels of a diverse array of antibiotics, to monitor the dynamics of the SOS response and study expression of SOS and methyl mismatch repair (MMR) genes.
45. Friedman N., Vardi S., Ronen M., Alon U., and Stavans J. Precise temporal modulation in the response of the SOS DNA repair network in individual bacteria. PLoS Biol 3 (2005) e238
46. Courcelle J., Khodursky A., Peter B., Brown P.O., and Hanawalt P.C. Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli. Genetics 158 (2001) 41-64
47. Napolitano R., Janel-Bintz R., Wagner J., and Fuchs R.P. All three SOS-inducible DNA polymerases (pol II, pol IV and pol V) are involved in induced mutagenesis. EMBO J 19 (2000) 6259-6265
48. Yang W., and Woodgate R. What a difference a decade makes: insights into translesion DNA synthesis. Proc Natl Acad Sci U S A 104 (2007) 15591-15598
49. Wagner J., Etienne H., Janel-Bintz R., and Fuchs R.P. Genetics of mutagenesis in E. coli: various combinations of translesion polymerases (pol II, IV and V) deal with lesion/sequence context diversity. DNA Repair (Amst) 1 (2002) 159-167
50. Tang M., Pham P., Shen X., Taylor J.S., O'Donnell M., Woodgate R., and Goodman M.F. Roles of E. coli DNA polymerases IV and V in lesion-targeted and untargeted SOS mutagenesis. Nature 404 (2000) 1014-1018
51. Jarosz D.F., Beuning P.J., Cohen S.E., and Walker G.C. Y-family DNA polymerases in Escherichia coli. Trends Microbiol 15 (2007) 70-77. A thorough review that discusses the transcriptional regulation, mutagenic potential, and mechanistic details of the error-prone, Y-family DNA polymerases pol IV (DinB) and pol V (UmuDC).
52. Schneider S., Schorr S., and Carell T. Crystal structure analysis of DNA lesion repair and tolerance mechanisms. Curr Opin Struct Biol 19 (2009) 87-95
53. •].
54. •].
55. •], this study describes observations made in both E. coli and S. aureus that β-lactam antibiotics, which do not directly damage DNA, can activate expression of the SOS response and SOS-related genes, which are most efficiently induced by genotoxic stress.
56. Goerke C., Koller J., and Wolz C. Ciprofloxacin and trimethoprim cause phage induction and virulence modulation in Staphylococcus aureus. Antimicrob Agents Chemother 50 (2006) 171-177
57. Gon S., and Beckwith J. Ribonucleotide reductases: influence of environment on synthesis and activity. Antioxid Redox Signal 8 (2006) 773-780
58. Beckman K.B., and Ames B.N. Oxidative decay of DNA. J Biol Chem 272 (1997) 19633-19636
59. Neeley W.L., Delaney S., Alekseyev Y.O., Jarosz D.F., Delaney J.C., Walker G.C., and Essigmann J.M. DNA polymerase V allows bypass of toxic guanine oxidation products in vivo. J Biol Chem 282 (2007) 12741-12748. This paper describes a study which measured the ability of several translesion synthesis mutant strains of E. coli to bypass a variety of oxidative DNA lesions, as well as the fidelity with which these mutant strains repaired the oxidative damage. Results showed that pol V is the primary translesion synthesis and oxidative damage repair DNA polymerase in vivo, but does so in a highly error-prone yet consistent manner that is partially mitigated by pol II activity.
60. McCullough A.K., Dodson M.L., and Lloyd R.S. Initiation of base excision repair: glycosylase mechanisms and structures. Annu Rev Biochem 68 (1999) 255-285
61. Cunningham R.P. DNA glycosylases. Mutat Res 383 (1997) 189-196
62. Mol C.D., Parikh S.S., Putnam C.D., Lo T.P., and Tainer J.A. DNA repair mechanisms for the recognition and removal of damaged DNA bases. Annu Rev Biophys Biomol Struct 28 (1999) 101-128
63. David S.S., O'Shea V.L., and Kundu S. Base-excision repair of oxidative DNA damage. Nature 447 (2007) 941-950
64. Loeb L.A., and Preston B.D. Mutagenesis by apurinic/apyrimidinic sites. Annu Rev Genet 20 (1986) 201-230
65. Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Br J Exp Pathol 10 (1929) 226-236
66. •].
67. •], this study describes the development of fluorescence-based assays for measuring the ATPase activity of RecA, and the rational design of a small peptide inhibitor of RecA that can bind to this critical regulator of the SOS response and inhibit its activation.
68. Koutsolioutsou A., Pena-Llopis S., and Demple B. Constitutive soxR mutations contribute to multiple-antibiotic resistance in clinical Escherichia coli isolates. Antimicrob Agents Chemother 49 (2005) 2746-2752