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Chapter 28 : Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance

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Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance, Page 1 of 2

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Abstract:

The majority of antibiotics in clinical and agricultural use are derived from secondary metabolites of bacteria, fungi, and plants. This chapter discusses the roles of redox chemical biology in antibiotic action and resistance. Bleomycin is a glycopeptide anticancer antibiotic produced by . Antimicrobial toxicity is dependent on the reduction of the nitro group via electron transport components, generating a nitro anion radical and breakdown compounds such as nitroso and hydroxylamine derivatives. The nitro anion radicals generated through the reduction by ferredoxin or flavodoxin, may oxidize from the presence of molecular oxygen. Bacterial killing was attenuated by the addition of the iron chelator 2,2'-dipyridyl and the radical scavenger thiourea. The physiological state of microbes also has an important role in reactive oxygen species (ROS) and antibiotic action. in liquid culture was more susceptible to oxidative stress generated by the antibiotics ceftazidime or piperacillin than during biofilm growth. MexR is a stable homodimer and functions as a transcriptional repressor and is a member of the MarA family transcriptional regulators. Redox and ROS have long been underexplored in antibiotic action and resistance but studies over the past decade have unequivocally demonstrated their importance in this field.

Citation: Radhi I, Wright G. 2011. Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance, p 461-471. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch28

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Figures

Image of Figure 1.
Figure 1.

Structure of bleomycin. The arrows highlight the metal binding ligands.

Citation: Radhi I, Wright G. 2011. Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance, p 461-471. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch28
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Image of Figure 2.
Figure 2.

Reductive activation of metronidazole.

Citation: Radhi I, Wright G. 2011. Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance, p 461-471. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch28
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Image of Figure 3.
Figure 3.

Proposed scheme for bactericidal antibiotic induction of cell death.

Citation: Radhi I, Wright G. 2011. Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance, p 461-471. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch28
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Image of Figure 4.
Figure 4.

Reductive activation of mitomycin C.

Citation: Radhi I, Wright G. 2011. Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance, p 461-471. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch28
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Image of Figure 5.
Figure 5.

TetX-mediated inactivation of tigecycline.

Citation: Radhi I, Wright G. 2011. Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance, p 461-471. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch28
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Image of Figure 6.
Figure 6.

The fluoroquinolone antibiotic ciprofloxacin.

Citation: Radhi I, Wright G. 2011. Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance, p 461-471. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch28
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Image of Figure 7.
Figure 7.

Structures of the pigmented antibiotics (A) pyocyanin and (B) actinorhodin.

Citation: Radhi I, Wright G. 2011. Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance, p 461-471. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch28
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