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

Authors: Inas J. Radhi1, Gerard D. Wright2
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Affiliations: 1: Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, 1200 Main St. W, McMaster University, Hamilton, ON L8N 3Z5, Canada; 2: Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, 1200 Main St. W, McMaster University, Hamilton, ON L8N 3Z5, Canada
Content Type: Monograph
Publication Year: 2011

Category: Microbial Genetics and Molecular Biology

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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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Redox Mechanisms and Reactive Oxygen Species in Antibiotic Action and Resistance
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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
/content/10.1128/9781555816841.ch28.ch28fig01
Figure 1.
Structure of bleomycin. The arrows highlight the metal binding ligands.
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10.1128/9781555816841/f0462-01.gif
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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Figure 2.
Reductive activation of metronidazole.
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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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Figure 3.
Proposed scheme for bactericidal antibiotic induction of cell death.
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10.1128/9781555816841/f0463-01.gif
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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Figure 4.
Reductive activation of mitomycin C.
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10.1128/9781555816841/f0465-01.gif
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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Figure 5.
TetX-mediated inactivation of tigecycline.
10.1128/9781555816841/f0466-01_thmb.gif
10.1128/9781555816841/f0466-01.gif
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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Figure 6.
The fluoroquinolone antibiotic ciprofloxacin.
10.1128/9781555816841/f0467-01_thmb.gif
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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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Figure 7.
Structures of the pigmented antibiotics (A) pyocyanin and (B) actinorhodin.
10.1128/9781555816841/f0468-01_thmb.gif
10.1128/9781555816841/f0468-01.gif
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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