Unraveling the physiological complexities of antibiotic lethality

Annual Review of Pharmacology and Toxicology

Volumn 55, Issue , 2015, Pages 313-332

  Dwyer, Daniel J ^a   Collins, James J ^b,c,d   Walker, Graham C ^e  

^a Bldg 142   (United States)

^b Boston University   (United States)

^c HARVARD UNIVERSITY   (United States)

^d BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Antibiotics; Cell death; Metabolism; Pathogens; Reactive oxygen species

Indexed keywords

ANTIBIOTIC AGENT; HYDROGEN SULFIDE; HYDROPEROXIDE; NITRIC OXIDE; REACTIVE OXYGEN METABOLITE; ANTIINFECTIVE AGENT; HYDROGEN PEROXIDE; NUCLEOTIDE; OXIDIZING AGENT;

BACTERIAL CELL; BACTERICIDAL ACTIVITY; DRUG EFFICACY; DRUG TARGETING; LETHALITY; MUTAGENESIS; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; SYSTEMS BIOLOGY; ANIMAL; ANTIBIOTIC RESISTANCE; BACTERIUM; DRUG EFFECTS; GENETICS; HUMAN; METABOLISM; MICROBIAL VIABILITY; OXIDATION REDUCTION REACTION;

BACTERIA (MICROORGANISMS);

ANIMALS; ANTI-BACTERIAL AGENTS; BACTERIA; DRUG RESISTANCE, BACTERIAL; HUMANS; HYDROGEN PEROXIDE; HYDROGEN SULFIDE; MICROBIAL VIABILITY; MUTAGENESIS; NITRIC OXIDE; NUCLEOTIDES; OXIDANTS; OXIDATION-REDUCTION; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; SYSTEMS BIOLOGY;

EID: 84920842454     PISSN: 03621642     EISSN: 15454304     Source Type: Book Series    
DOI: 10.1146/annurev-pharmtox-010814-124712     Document Type: Review

References (141)

1. Cent. Dis. Control Prev. 2013. Antibiotic resistance threats in the United States, 2013. Rep., Cent. Dis. Control Prev., Atlanta, GA
2. Wright GD. 2007. The antibiotic resistome: the nexus of chemical and genetic diversity. Nat. Rev. Microbiol. 5:175-86
3. Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, et al. 2008. The epidemic of antibioticresistant infections: A call to action for the medical community from the Infectious Diseases Society of America. Clin. Infect. Dis. 46:155-64
4. Fischbach MA, Walsh CT. 2009. Antibiotics for emerging pathogens. Science 325:1089-93
5. Davies J, Davies D. 2010. Origins and evolution of antibiotic resistance. Microbiol. Mol. Biol. Rev. 74:417-33
6. Piddock LJV. 2012. The crisis of no new antibiotics-what is the way forward? Lancet Infect. Dis. 12:249-53
7. Editoria l. 2013. The antibiotic alarm. Nature 495:141
8. Drlica K, Perlin DS. 2011. Antibiotic Resistance: Understanding and Responding to an Emerging Crisis. Upper Saddle River, NJ: FT
9. Walsh C. 2003. Antibiotics: Actions, Origins, Resistance. Washington, DC: ASM
10. Kohanski MA, Dwyer DJ, Collins JJ. 2010. How antibiotics kill bacteria: from targets to networks. Nat. Rev. Microbiol. 8:423-35
11. Ezraty B, Vergnes A, Banzhaf M, Duverger Y, Huguenot A, et al. 2013. Fe-S cluster biosynthesis controls uptake of aminoglycosides in a ROS-less death pathway. Science 340:1583-87
12. Keren I, Wu Y, Inocencio J, Mulcahy LR, Lewis K. 2013. Killing by bactericidal antibiotics does not depend on reactive oxygen species. Science 339:1213-16
13. Liu Y, Imlay JA. 2013. Cell death from antibiotics without the involvement of reactive oxygen species. Science 339:1210-13
14. Greenberg JT, Monach P, Chou JH, Josephy PD, Demple B. 1990. Positive control of a global antioxidant defense regulon activated by superoxide-generating agents in Escherichia coli. Proc. Natl. Acad. Sci. USA 87:6181-85
15. Arriaga-Alba M, Rivera-Sanchez R, Parra-Cervantes G, Barro-Moreno F, Flores-Paz R, Garcia-Jimenez E. 2000. Antimutagenesis of β-carotene to mutations induced by quinolone on Salmonella typhimurium. Arch. Med. Res. 31:156-61
16. Becerra MC, Albesa I. 2002. Oxidative stress induced by ciprofloxacin in Staphylococcus aureus. Biochem. Biophys. Res. Commun. 297:1003-7
17. Utaida S, Dunman PM, Macapagal D, Murphy E, Projan SJ, et al. 2003. Genome-wide transcriptional profiling of the response of Staphylococcus aureus to cell-wall-active antibiotics reveals a cell-wall-stress stimulon. Microbiology 149:2719-32
18. Storz GZM. 2000. Oxidative stress. In Bacterial Stress Responses, ed. RHengge-Aronis, GStorz, pp. 47-59. Washington, DC: ASM
19. Waddell SJ, Stabler RA, Laing K, Kremer L, Reynolds RC, Besra GS. 2004. The use of microarray analysis to determine the gene expression profiles of Mycobacterium tuberculosis in response to anti-bacterial compounds. Tuberculosis 84:263-74
20. Albesa I, Becerra MC, Battan PC, Paez PL. 2004. Oxidative stress involved in the antibacterial action of different antibiotics. Biochem. Biophys. Res. Commun. 317:605-9
21. Becerra MC, Paez PL, Lar overe LE, Albesa I. 2006. Lipids and DNA oxidation in Staphylococcus aureus as a consequence of oxidative stress generated by ciprofloxacin. Mol. Cell Biochem. 285:29-34
22. Goswami M, Mangoli SH, Jawali N. 2006. Involvement of reactive oxygen species in the action of ciprofloxacin against Escherichia coli. Antimicrob. Agents Chemother. 50:949-54
23. Malik M, Hussain S, Drlica K. 2007. Effect of anaerobic growth on quinolone lethality with Escherichia coli. Antimicrob. Agents Chemother. 51:28-34
24. Lewin CS, Morrissey I, Smith JT. 1991. The mode of action of quinolones: the paradox in activity of low and high concentrations and activity in the anaerobic environment. Eur. J. Clin. Microbiol. Infect. Dis. 10:240-48
25. Morrissey I, Smith JT. 1994. The importance of oxygen in the killing of bacteria by ofloxacin and ciprofloxacin. Microbios 79:43-53
26. Kitano H. 2002. Systems biology: A brief overview. Science 295:1662-64
27. Brazas MD, Hancock RE. 2005. Using microarray gene signatures to elucidate mechanisms of antibiotic action and resistance. Drug Discov. Today 10:1245-52
28. Dwyer DJ, Kohanski MA, Hayete B, Collins JJ. 2007. Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli. Mol. Syst. Biol. 3:91
29. Hayes F. 2003. Toxins-antitoxins: plasmid maintenance, programmed cell death, and cell cycle arrest. Science 301:1496-99
30. Drlica K, Zhao X. 1997. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol. Mol. Biol. Rev. 61:377-92
31. Setsukinai K, Urano Y, Kakinuma K, Majima HJ, Nagano T. 2003. Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J. Biol. Chem. 278:3170-75
32. Imlay JA, Chin SM, Linn S. 1988. Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science 240:640-42
33. Demple B. 1996. Redox signaling and gene control in the Escherichia coli soxRS oxidative stress regulon- A review. Gene 179:53-57
34. McHugh JP, Rodrguez-Quinones F, Abdul-Tehrani H, Svistunenko DA, Poole RK, et al. 2003. Global iron-dependent gene regulation in Escherichia coli: A new mechanism for iron homeostasis. J. Biol. Chem. 278:29478-86
35. Zheng L, Cash VL, Flint DH, Dean DR. 1998. Assembly of iron-sulfur clusters: identification of an iscSUA-hscBA-fdx gene cluster from Azotobacter vinelandii. J. Biol. Chem. 273:13264-72
36. Roche B, Aussel L, Ezraty B, Mandin P, Py B, Barras F. 2013. Iron/sulfur proteins biogenesis in prokaryotes: formation, regulation and diversity. Biochim. Biophys. Acta 1827:455-69
37. Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, Collins JJ. 2007. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130:797-810
38. Helling RB, Kukora JS. 1971. Nalidixic acid-resistant mutants of Escherichia coli deficient in isocitrate dehydrogenase. J. Bacteriol. 105:1224-26
39. Akhova AV, Tkachenko AG. 2014. The ATP/ADP alteration as a sign of the oxidative stress development in Escherichia coli cells under antibiotic treatment. FEMS Microbiol. Lett. 353:69-76
40. Wang X, Zhao X. 2009. Contribution of oxidative damage to antimicrobial lethality. Antimicrob. Agents Chemother. 53:1395-402
41. Seaver LC, Imlay JA. 2001. Alkyl hydroperoxide reductase is the primary scavenger of endogenous hydrogen peroxide in Escherichia coli. J. Bacteriol. 183:7173-81
42. Mosel M, Li L, Drlica K, Zhao X. 2013. Superoxide-mediated protection of Escherichia coli from antimicrobials. Antimicrob. Agents Chemother. 57:5755-59
43. Girgis HS, Hottes AK, Tavazoie S. 2009. Genetic architecture of intrinsic antibiotic susceptibility. PLOS ONE 4:e5629
44. Yamamoto N, Nakahigashi K, Nakamichi T, Yoshino M, Takai Y, et al. 2009. Update on the Keio collection of Escherichia coli single-gene deletion mutants. Mol. Syst. Biol. 5:335
45. Liu A, Tran L, Becket E, Lee K, Chinn L, et al. 2010. Antibiotic sensitivity profiles determined with an Escherichia coli gene knockout collection: generating an antibiotic bar code. Antimicrob. Agents Chemother. 54:1393-403
46. Kohanski MA, Dwyer DJ, Wierzbowski J, Cottarel G, Collins JJ. 2008. Mistranslation of membrane proteins and two-component system activation trigger antibiotic-mediated cell death. Cell 135:679-90
47. Wickner W, Schekman R. 2005. Protein translocation across biological membranes. Science 310:1452-56
48. Ruiz N, Silhavy TJ. 2005. Sensing external stress: watchdogs of the Escherichia coli cell envelope. Curr. Opin. Microbiol. 8:122-26
49. Dukan S, Farewell A, Ballesteros M, Taddei F, Radman M, Nystrom T. 2000. Protein oxidation in response to increased transcriptional or translational errors. Proc. Natl. Acad. Sci. USA 97:5746-49
50. Iuchi S, Furlong D, Lin ECC. 1989. Differentiation of arcA, arcB, and cpxA mutant phenotypes of Escherichia coli by sex pilus formation and enzyme regulation. J. Bacteriol. 171:2889-93
51. Ronson CW, Nixon BT, Ausubel FM. 1987. Conserved domains in bacterial regulatory proteins that respond to environmental stimuli. Cell 49:579-81
52. Mahoney TF, Silhavy TJ. 2013. The Cpx stress response confers resistance to some, but not all, bactericidal antibiotics. J. Bacteriol. 195:1869-74
53. Raivio TL, Silhavy TJ. 1997. Transduction of envelope stress in Escherichia coli by theCpx two-component system. J. Bacteriol. 179:7724-33
54. Raivio TL, Leblanc SK, Price NL. 2013. The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity. J. Bacteriol. 195:2755-67
55. Raivio TL. 2013. Everything old is new again: an update on current research on the Cpx envelope stress response. Biochim. Biophys. Acta 1843:1529-41
56. Dorsey-Oresto A, Lu T, Mosel M, Wang X, Salz T, et al. 2013. YihE kinase is a central regulator of programmed cell death in bacteria. Cell Rep. 3:528-37
57. Foti JJ, Devadoss B, Winkler JA, Collins JJ, Walker GC. 2012. Oxidation of the guanine nucleotide pool underlies cell death by bactericidal antibiotics. Science 336:315-19
58. Yeom J, Imlay JA, Park W. 2010. Iron homeostasis affects antibiotic-mediated cell death in Pseudomonas species. J. Biol. Chem. 285:22689-95
59. Daung-nkern J, Vattanaviboon P, Mongkolsuk S. 2010. Inactivation of nfuA enhances susceptibility of Pseudomonas aeruginosa to fluoroquinolone antibiotics. J. Antimicrob. Chemother. 65:1831-32
60. Nguyen D, Joshi-Datar A, Lepine F, Bauerle E, Olakanmi O, et al. 2011. Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science 334:982-86
61. Khakimova M, Ahlgren HG, Harrison JJ, English AM, Nguyen D. 2013. The stringent response controls catalases in Pseudomonas aeruginosa and is required for hydrogen peroxide and antibiotic tolerance. J. Bacteriol. 195:2011-20
62. Kim JJ, Lee HM, Shin DM, Kim W, Yuk JM, et al. 2012. Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action. Cell Host Microbe 11:457-68
63. Pandey R, Rodriguez GM. 2012. A ferritin mutant of Mycobacterium tuberculosis is highly susceptible to killing by antibiotics and is unable to establish a chronic infection in mice. Infect. Immun. 80:3650-59
64. Grant SS, Kaufmann BB, Chand NS, Haseley N, Hung DT. 2012. Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals. Proc. Natl. Acad. Sci. USA 109:12147-52
65. Mukherjee P, Sureka K, Datta P, Hossain T, Barik S, et al. 2009. Novel role of Wag31 in protection of mycobacteria under oxidative stress. Mol. Microbiol. 73:103-19
66. Calhoun LN, Kwon YM. 2011. The ferritin-like protein Dps protects Salmonella enterica serotype Enteritidis from the Fenton-mediated killing mechanism of bactericidal antibiotics. Int. J. Antimicrob. Agents 37:261-65
67. Frawley ER, Crouch ML, Bingham-Ramos LK, Robbins HF, Wang W, et al. 2013. Iron and citrate export by a major facilitator superfamily pump regulates metabolism and stress resistance in Salmonella Typhimurium. Proc. Natl. Acad. Sci. USA 110:12054-59
68. Krawczyk-Balska A, Marchlewicz J, Dudek D, Wasiak K, Samluk A. 2012. Identification of a ferritinlike protein of Listeria monocytogenes as a mediator of β-lactam tolerance and innate resistance to cephalosporins. BMC Microbiol. 12:278
69. Paez PL, Becerra MC, Albesa I. 2010. Antioxidativemechanisms protect resistant strains of Staphylococcus aureus against ciprofloxacin oxidative damage. Fundam. Clin. Pharmacol. 24:771-76
70. Liu Y, Liu X, Qu Y, Wang X, Li L, Zhao X. 2012. Inhibitors of reactive oxygen species accumulation delay and/or reduce the lethality of several antistaphylococcal agents. Antimicrob. Agents Chemother. 56:6048-50
71. Ferrandiz MJ, de la Campa AG. 2014. The fluoroquinolone levofloxacin triggers the transcriptional activation of iron transport genes that contribute to cell death in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 58:247-57
72. Soares NC, Cabral MP, Gayoso C, Mallo S, Rodriguez-Velo P, et al. 2010. Associating growth-phaserelated changes in the proteome of Acinetobacter baumannii with increased resistance to oxidative stress. J. Proteome Res. 9:1951-64
73. Aranda J, Bardina C, Beceiro A, Rumbo S, Cabral MP, et al. 2011. Acinetobacter baumannii RecA protein in repair of DNA damage, antimicrobial resistance, general stress response, and virulence. J. Bacteriol. 193:3740-47
74. Sampson TR, Liu X, Schroeder MR, Kraft CS, Burd EM, Weiss DS. 2012. Rapid killing of Acinetobacter baumannii by polymyxins is mediated by a hydroxyl radical death pathway. Antimicrob. Agents Chemother. 56:5642-49
75. Perez F, Hujer AM, Hujer KM, Decker BK, Rather PN, Bonomo RA. 2007. Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 51:3471-84
76. Hoskins J, Alborn WE Jr, Arnold J, Blaszczak LC, Burgett S, et al. 2001. Genome of the bacterium Streptococcus pneumoniae strain R6. J. Bacteriol. 183:5709-17
77. Tettelin H, Nelson KE, Paulsen IT, Eisen JA, Read TD, et al. 2001. Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293:498-506
78. Webber MA, Coldham NG, Woodward MJ, Piddock LJV. 2008. Proteomic analysis of triclosan resistance in Salmonella enterica serovar Typhimurium. J. Antimicrob. Chemother. 62:92-97
79. Chittezham Thomas V, Kinkead LC, Janssen A, Schaeffer CR, Woods KM, et al. 2013. A dysfunctional tricarboxylic acid cycle enhances fitness of Staphylococcus epidermidis during β-lactam stress. MBio 4:e00437-13
80. Hao Z, Lou H, Zhu R, Zhu J, Zhang D, et al. 2014. The multiple antibiotic resistance regulator MarR is a copper sensor in Escherichia coli. Nat. Chem. Biol. 10:21-28
81. Zhao BS, Liang Y, Song Y, Zheng C, Hao Z, Chen PR. 2010. A highly selective fluorescent probe for visualization of organic hydroperoxides in living cells. J. Am. Chem. Soc. 132:17065-67
82. de la Cruz Rodrguez LC, Faras RN, Massa EM. 1990. Damage of Escherichia coli cells by tbutylhydroperoxide involves the respiratory chain but is independent of the presence of oxygen. Biochim. Biophys. Acta 1015:510-16
83. Rodriguez-Montelongo L, de la Cruz Rodrguez LC, Faras RN, Massa EM. 1993. Membrane-associated redox cycling of coppermediates hydroperoxide toxicity in Escherichia coli. Biochim. Biophys. Acta 1144:77-84
84. Gusarov I, Nudler E. 2005. NO-mediated cytoprotection: instant adaptation to oxidative stress in bacteria. Proc. Natl. Acad. Sci. USA 102:13855-60
85. Shatalin K, Gusarov I, Avetissova E, Shatalina Y, McQuade LE, et al. 2008. Bacillus anthracis-derived nitric oxide is essential for pathogen virulence and survival in macrophages. Proc. Natl. Acad. Sci. USA 105:1009-13
86. Gusarov I, Shatalin K, Starodubtseva M, Nudler E. 2009. Endogenous nitric oxide protects bacteria against a wide spectrum of antibiotics. Science 325:1380-84
87. van Sorge NM, Beasley FC, Gusarov I, Gonzalez DJ, vonKockritz-Blickwede M, et al. 2013. Methicillinresistant Staphylococcus aureus bacterial nitric-oxide synthase affects antibiotic sensitivity and skin abscess development. J. Biol. Chem. 288:6417-26
88. Holden JK, Li H, Jing Q, Kang S, Richo J, et al. 2013. Structural and biological studies on bacterial nitric oxide synthase inhibitors. Proc. Natl. Acad. Sci. USA 110:18127-31
89. Shatalin K, Shatalina E, Mironov A, Nudler E. 2011. H2S: A universal defense against antibiotics in bacteria. Science 334:986-90
90. Traub WH, Kleber I. 1975. Characterization of two H2S-producing, multiple drug-resistant isolates of Escherichia coli from clinical urine specimens. Pathol. Microbiol. 43:10-16
91. Jones RT, Thai LP, Silver RP. 1978. Genetic and molecular characterization of an Escherichia coli plasmid coding for hydrogen sulfide production and drug resistance. Antimicrob. Agents Chemother. 14:765-70
92. Neeley WL, Essigmann JM. 2006. Mechanisms of formation, genotoxicity, and mutation of guanine oxidation products. Chem. Res. Toxicol. 19:491-505
93. Yamada M, Nunoshiba T, Shimizu M, Gruz P, Kamiya H, et al. 2006. Involvement of Y-family DNA polymerases in mutagenesis caused by oxidized nucleotides in Escherichia coli. J. Bacteriol. 188:4992-95
94. Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T. 2006. DNA Repair and Mutagenesis. Washington, DC: ASM. 2nd ed.
95. Bonura T, Town CD, Smith KC, Kaplan HS. 1975. The influence of oxygen on the yield of DNA double-strand breaks in X-irradiated Escherichia coli K-12. Radiat. Res. 63:567-77
96. Ward JF, Evans JW, Limoli CL, Calabro-Jones PM. 1987. Radiation and hydrogen peroxide induced free radical damage to DNA. Br. J. Cancer Suppl. 8:105-12
97. Brenner DJ, Ward JF. 1992. Constraints on energy deposition and target size of multiply damaged sites associated with DNA double-strand breaks. Int. J. Radiat. Biol. 61:737-48
98. Zhao J, Winkler ME. 2000. Reduction of GCTA transversion mutation by overexpression of MutS in Escherichia coli K-12. J. Bacteriol. 182:5025-28
99. Dwyer DJ, Belenky P, Yang JH, MacDonald IC, Martell JD, et al. 2014. Antibiotics induce redox-related physiological alterations as part of their lethality. Proc. Natl. Acad. Sci. USA 111:E2100-9
100. Sekiguchi T, Ito R, Hayakawa H, Sekiguchi M. 2013. Elimination and utilization of oxidized guanine nucleotides in the synthesis of RNA and its precursors. J. Biol. Chem. 288:8128-35
101. Taddei F, Hayakawa H, Bouton M, Cirinesi A, Matic I, et al. 1997. Counteraction by MutT protein of transcriptional errors caused by oxidative damage. Science 278:128-30
102. Imlay JA. 2013. The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium. Nat. Rev. Microbiol. 11:443-54
103. Weaver J, Pollack S. 1989. Low-Mr iron isolated from guinea pig reticulocytes as AMP-Fe and ATP-Fe complexes. Biochem. J. 261:787-92
104. Floyd RA. 1983. Direct demonstration that ferrous ion complexes of di- and triphosphate nucleotides catalyze hydroxyl free radical formation from hydrogen peroxide. Arch. Biochem. Biophys. 225:263-70
105. Rush JD, Maskos Z, Koppenol WH. 1990. Reactions of iron(II) nucleotide complexes with hydrogen peroxide. FEBS Lett. 261:121-23
106. Richter Y, Fischer B. 2003. Characterization and elucidation of coordination requirements of adenine nucleotides complexes with Fe(II) ions. Nucleosides Nucleotides Nucleic Acids 22:1757-80
107. Yamamoto N, Koga N, Nagaoka M. 2012. Ferryl-oxo species produced from Fentons reagent via a two-step pathway: minimum free-energy path analysis. J. Phys. Chem. B 116:14178-82
108. Tkachenko AG, Akhova AV, Shumkov MS, Nesterova LY. 2012. Polyamines reduce oxidative stress in Escherichia coli cells exposed to bactericidal antibiotics. Res. Microbiol. 163:83-91
109. Winterbourn CC. 2008. Reconciling the chemistry and biology of reactive oxygen species. Nat. Chem. Biol. 4:278-86
110. Pursell ZF, McDonald JT, Mathews CK, Kunkel TA. 2008. Trace amounts of 8-oxo-dGTP in mitochondrial dNTP pools reduce DNA polymerase βreplication fidelity. Nucleic Acids Res. 36:2174-81
111. Gad H, Koolmeister T, Jemth AS, Eshtad S, Jacques SA, et al. 2014. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature 508:215-21
112. Huber KV, Salah E, Radic B, Gridling M, Elkins JM, et al. 2014. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature 508:222-27
113. Rai P, Onder TT, Young JJ, McFaline JL, Pang B, et al. 2009. Continuous elimination of oxidized nucleotides is necessary to prevent rapid onset of cellular senescence. Proc. Natl. Acad. Sci. USA 106:169-74
114. Rai P, Young JJ, Burton DG, Giribaldi MG, Onder TT, Weinberg RA. 2011. Enhanced elimination of oxidized guanine nucleotides inhibits oncogenic RAS-induced DNA damage and premature senescence. Oncogene 30:1489-96
115. De Luca G, Russo MT, Degan P, Tiveron C, Zijno A, et al. 2008. A role for oxidized DNA precursors in Huntingtons disease-like striatal neurodegeneration. PLOS Genet. 4:e1000266
116. Yamaguchi H, Kajitani K, Dan Y, Furuichi M, Ohno M, et al. 2006. MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1- methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Cell Death Differ. 13:551-63
117. Murakami Y, Ikeda Y, Yoshida N, Notomi S, Hisatomi T, et al. 2012. MutT homolog-1 attenuates oxidative DNA damage and delays photoreceptor cell death in inherited retinal degeneration. Am. J. Pathol. 181:1378-86
118. Kohanski MA, DePristo MA, Collins JJ. 2010. Sublethal antibiotic treatment leads tomultidrug resistance via radical-induced mutagenesis. Mol. Cell 37:311-20
119. Thi TD, L opez E, Rodrguez-Rojas A, Rodrguez-Beltran J, Couce A, et al. 2011. Effect of recA inactivation on mutagenesis of Escherichia coli exposed to sublethal concentrations of antimicrobials. J. Antimicrob. Chemother. 66:531-38
120. Gutierrez A, Laureti L, Crussard S, Abida H, Rodrguez-Rojas A, et al. 2013. β-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity. Nat. Commun. 4:1610
121. Yamada M, Shimizu M, Katafuchi A, Gruz P, Fujii S, et al. 2012. Escherichia coli DNA polymerase III is responsible for the high level of spontaneous mutations in mutT strains. Mol. Microbiol. 86:1364-75
122. Davies J, Spiegelman GB, Yim G. 2006. The world of subinhibitory antibiotic concentrations. Curr. Opin. Microbiol. 9:445-53
123. Kummerer K. 2003. Significance of antibiotics in the environment. J. Antimicrob. Chemother. 52:5-7
124. Baharoglu Z, Babosan A, Mazel D. 2013. Identification of genes involved in low aminoglycoside-induced SOS response in Vibrio cholerae: A role for transcription stalling and Mfd helicase. Nucleic Acids Res. 42:2366-79
125. Kang TM, Yuan J, Nguyen A, Becket E, Yang H, Miller JH. 2012. The aminoglycoside antibiotic kanamycin damages DNA bases in Escherichia coli: caffeine potentiates the DNA-damaging effects of kanamycin while suppressing cell killing by ciprofloxacin in Escherichia coli and Bacillus anthracis. Antimicrob. Agents Chemother. 56:3216-23
126. Ling J, Cho C, Guo LT, Aerni HR, Rinehart J, Soll D. 2012. Protein aggregation caused by aminoglycoside action is prevented by a hydrogen peroxide scavenger. Mol. Cell 48:713-22
127. Poole K. 2012. Bacterial stress responses as determinants of antimicrobial resistance. J. Antimicrob. Chemother. 67:2069-89
128. Jang S, Imlay JA. 2010. Hydrogen peroxide inactivates the Escherichia coli Isc iron-sulphur assembly system, and OxyR induces the Suf system to compensate. Mol. Microbiol. 78:1448-67
129. Nachin L, Loiseau L, Expert D, Barras F. 2003. SufC: an unorthodox cytoplasmic ABC/ATPase required for [Fe-S] biogenesis under oxidative stress. EMBO J. 22:427-37
130. Yeo WS, Lee JH, Lee KC, Roe JH. 2006. IscR acts as an activator in response to oxidative stress for the suf operon encoding Fe-S assembly proteins. Mol. Microbiol. 61:206-18
131. Nakayashiki T, Saito N, Takeuchi R, Kadokura H, Nakahigashi K, et al. 2013. The tRNA thiolation pathway modulates the intracellular redox state in Escherichia coli. J. Bacteriol. 195:2039-49
132. Wang X, Zhao X, Malik M, Drlica K. 2010. Contribution of reactive oxygen species to pathways of quinolone-mediated bacterial cell death. J. Antimicrob. Chemother. 65:520-24
133. Lu TK, Collins JJ. 2009. Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy. Proc. Natl. Acad. Sci. USA 106:4629-34
134. Brynildsen MP, Winkler JA, Spina CS, MacDonald IC, Collins JJ. 2013. Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production. Nat. Biotechnol. 31:160-65
135. Hwang IS, Hwang JH, Choi H, Kim KJ, Lee DG. 2012. Synergistic effects between silver nanoparticles and antibiotics and the mechanisms involved. J. Med. Microbiol. 61:1719-26
136. Hwang IS, Hwang JS, Hwang JH, Choi H, Lee E, et al. 2013. Synergistic effect and antibiofilm activity between the antimicrobial peptide coprisin and conventional antibiotics against opportunistic bacteria. Curr. Microbiol. 66:56-60
137. Choi H, Lee DG. 2012. Synergistic effect of antimicrobial peptide arenicin-1 in combination with antibiotics against pathogenic bacteria. Res. Microbiol. 163:479-86
138. Choi H, Lee DG. 2012. Antimicrobial peptide pleurocidin synergizes with antibiotics through hydroxyl radical formation and membrane damage, and exerts antibiofilm activity. Biochim. Biophys. Acta 1820:1831-38
139. Morones-Ramirez JR, Winkler JA, Spina CS, Collins JJ. 2013. Silver enhances antibiotic activity against gram-negative bacteria. Sci. Transl. Med. 5:190ra81
140. Molina-Quiroz RC, Munoz-Villagran CM, de la Torre E, Tantalean JC, Vasquez CC, Perez-Donoso JM. 2012. Enhancing the antibiotic antibacterial effect by sub lethal tellurite concentrations: tellurite and cefotaxime act synergistically in Escherichia coli. PLOS ONE 7:e35452
141. Molina-Quiroz RC, Loyola DE, Munoz-Villagran CM, Quatrini R, Vasquez CC, Perez-Donoso JM. 2013. DNA, cell wall and general oxidative damage underlie the tellurite/cefotaxime synergistic effect in Escherichia coli. PLOS ONE 8:e79499