Role of Reactive Oxygen Species in Antibiotic Action and Resistance

Overview

Journal Curr Opin Microbiol

Specialty Microbiology

Date 2009 Aug 4

PMID 19647477

Citations 168

Authors

Daniel J Dwyer

Michael A Kohanski

James J Collins

Affiliations

Soon will be listed here.

Abstract

The alarming spread of bacterial strains exhibiting resistance to current antibiotic therapies necessitates that we elucidate the specific genetic and biochemical responses underlying drug-mediated cell killing, so as to increase the efficacy of available treatments and develop new antibacterials. Recent research aimed at identifying such cellular contributions has revealed that antibiotics induce changes in metabolism that promote the formation of reactive oxygen species, which play a role in cell death. Here we discuss the relationship between drug-induced oxidative stress, the SOS response and their potential combined contribution to resistance development. Additionally, we describe ways in which these responses are being taken advantage to combat bacterial infections and arrest the rise of resistant strains.

Citing Articles

Disinfectants and one health review: The role of reactive oxygen species in the bactericidal activity of chlorine against .

Aljuwayd M, Malli I, Olson E, Ricke S, Rothrock Jr M, Kwon Y One Health. 2025; 20:100989.

PMID: 40035020 PMC: 11874720. DOI: 10.1016/j.onehlt.2025.100989.

Genetic adaptation to amoxicillin in Escherichia coli: The limited role of dinB and katE.

Teichmann L, Wenne M, Luitwieler S, Dugar G, Bengtsson-Palme J, Ter Kuile B PLoS One. 2025; 20(2):e0312223.

PMID: 39970152 PMC: 11838884. DOI: 10.1371/journal.pone.0312223.

Disruptions of Genes Encoding Ribose-5-Phosphate Isomerases in Increases Sensitivity of Bacteria to Antibiotics.

Seregina T, Shakulov R, Sklyarova S, Mironov A Cells. 2024; 13(22).

PMID: 39594664 PMC: 11592462. DOI: 10.3390/cells13221915.

Whole genome CRISPRi screening identifies druggable vulnerabilities in an isoniazid resistant strain of Mycobacterium tuberculosis.

Wang X, Jowsey W, Cheung C, Smart C, Klaus H, Seeto N Nat Commun. 2024; 15(1):9791.

PMID: 39537607 PMC: 11560980. DOI: 10.1038/s41467-024-54072-w.

Trehalose catalytic shift is an intrinsic factor in Mycobacterium tuberculosis that enhances phenotypic heterogeneity and multidrug resistance.

Eoh H, Lee J, Swanson D, Lee S, Dihardjo S, Lee G Res Sq. 2024; .

PMID: 39315249 PMC: 11419184. DOI: 10.21203/rs.3.rs-4999164/v1.

References

Girgis H, Hottes A, Tavazoie S . Genetic architecture of intrinsic antibiotic susceptibility. PLoS One. 2009; 4(5):e5629. PMC: 2680486. DOI: 10.1371/journal.pone.0005629. View

Yang W, Woodgate R . What a difference a decade makes: insights into translesion DNA synthesis. Proc Natl Acad Sci U S A. 2007; 104(40):15591-8. PMC: 2000391. DOI: 10.1073/pnas.0704219104. View

Neeley W, Delaney S, Alekseyev Y, Jarosz D, Delaney J, Walker G . DNA polymerase V allows bypass of toxic guanine oxidation products in vivo. J Biol Chem. 2007; 282(17):12741-8. DOI: 10.1074/jbc.M700575200. View

Loeb L, Preston B . Mutagenesis by apurinic/apyrimidinic sites. Annu Rev Genet. 1986; 20:201-30. DOI: 10.1146/annurev.ge.20.120186.001221. View

Imlay J, Chin S, Linn S . Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science. 1988; 240(4852):640-2. DOI: 10.1126/science.2834821. View

Ysern P, Clerch B, Castano M, Gibert I, Barbe J, Llagostera M . Induction of SOS genes in Escherichia coli and mutagenesis in Salmonella typhimurium by fluoroquinolones. Mutagenesis. 1990; 5(1):63-6. DOI: 10.1093/mutage/5.1.63. View

Maiques E, Ubeda C, Campoy S, Salvador N, Lasa I, Novick R . beta-lactam antibiotics induce the SOS response and horizontal transfer of virulence factors in Staphylococcus aureus. J Bacteriol. 2006; 188(7):2726-9. PMC: 1428414. DOI: 10.1128/JB.188.7.2726-2729.2006. View

Pomposiello P, Demple B . Redox-operated genetic switches: the SoxR and OxyR transcription factors. Trends Biotechnol. 2001; 19(3):109-14. DOI: 10.1016/s0167-7799(00)01542-0. View

McCullough A, Dodson M, Lloyd R . Initiation of base excision repair: glycosylase mechanisms and structures. Annu Rev Biochem. 2000; 68:255-85. DOI: 10.1146/annurev.biochem.68.1.255. View

10.

Jarosz D, Beuning P, Cohen S, Walker G . Y-family DNA polymerases in Escherichia coli. Trends Microbiol. 2007; 15(2):70-7. DOI: 10.1016/j.tim.2006.12.004. View

11.

Kohanski M, Dwyer D, Hayete B, Lawrence C, Collins J . A common mechanism of cellular death induced by bactericidal antibiotics. Cell. 2007; 130(5):797-810. DOI: 10.1016/j.cell.2007.06.049. View

12.

Imlay J . Pathways of oxidative damage. Annu Rev Microbiol. 2003; 57:395-418. DOI: 10.1146/annurev.micro.57.030502.090938. View

13.

Wright G . The antibiotic resistome: the nexus of chemical and genetic diversity. Nat Rev Microbiol. 2007; 5(3):175-86. DOI: 10.1038/nrmicro1614. View

14.

Friedman N, Vardi S, Ronen M, Alon U, Stavans J . Precise temporal modulation in the response of the SOS DNA repair network in individual bacteria. PLoS Biol. 2005; 3(7):e238. PMC: 1151601. DOI: 10.1371/journal.pbio.0030238. View

15.

Drlica K, Malik M . Fluoroquinolones: action and resistance. Curr Top Med Chem. 2003; 3(3):249-82. DOI: 10.2174/1568026033452537. View

16.

Mesak L, Miao V, Davies J . Effects of subinhibitory concentrations of antibiotics on SOS and DNA repair gene expression in Staphylococcus aureus. Antimicrob Agents Chemother. 2008; 52(9):3394-7. PMC: 2533449. DOI: 10.1128/AAC.01599-07. View

17.

Mol C, Parikh S, Putnam C, Lo T, Tainer J . DNA repair mechanisms for the recognition and removal of damaged DNA bases. Annu Rev Biophys Biomol Struct. 1999; 28:101-28. DOI: 10.1146/annurev.biophys.28.1.101. View

18.

Balasubramanian B, Pogozelski W, Tullius T . 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. 1998; 95(17):9738-43. PMC: 21406. DOI: 10.1073/pnas.95.17.9738. View

19.

Dwyer D, Kohanski M, Collins J . Networking opportunities for bacteria. Cell. 2008; 135(7):1153-6. PMC: 2728295. DOI: 10.1016/j.cell.2008.12.016. View

20.

Beaber J, Hochhut B, Waldor M . SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature. 2003; 427(6969):72-4. DOI: 10.1038/nature02241. View