Chapter 9 : Mechanisms of Resistance to NO-Related Antibacterial Activity

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Little more than a decade ago, it was discovered that an array of physiological processes ranging from vascular homeostasis to neurotransmission and immunity are regulated by endogenously produced nitric oxide (NO). This chapter focuses on some of the recently elucidated strategies by which bacteria cope with the cytotoxic effects of NO and its redox congeners. Microbes, particularly pathogenic species, have coapted previously existing mechanisms and evolved novel strategies to avoid NO exposure or detoxify nitrogen oxides. The SoxRS and OxyR regulons are well characterized regarding their roles in resistance of enteric bacteria to oxidative stress, but both appear to be involved in resistance to reactive nitrogen species as well. Certain genes belonging to the SoxRS or OxyR regulons such as (glucose-6-phosphate dehydrogenase) and (alkyl hydroperoxide reductase) do appear to play a role in the resistance of and to NO-dependent cytotoxicity, but this may reflect the incomplete dependence of these loci on SoxRS or OxyR for expression. The reducing potential of thioredoxin reductase is regenerated at the expense of thioredoxin and NADPH. Although a theoretically attractive defense mechanism, the role of thioredoxin reductase in the resistance of pathogenic organisms to NO-related cytotoxicity remains to be tested experimentally. A more complete comprehension of mechanisms of resistance to NO-related antibacterial activities will shed new light in understanding infectious processes and lead to the discovery and application of new therapies.

Citation: Vazquez-Torres A, Fang F. 2000. Mechanisms of Resistance to NO-Related Antibacterial Activity, p 131-142. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch9

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Microbial defenses against reactive oxygen and nitrogen intermediates. Abbreviations: SOD, superoxide dismutase; Hmp, flavohemoprotein; GSH, glutathione; HC, homocysteine; FumC, resistant fumarase; Ftn, ferritin; Kat, catalase; Ahp, alkyl hydroperoxide reductase; Gor, glutathione reductase; Zwf, glucose-6-phosphate dehydrogenase; Nfo, endonuclease IV; OxyR, HO response regulator; SoxS, superoxide response regulator; RecBC, exonuclease V. Adapted from reference 31 with copyright permission by the .

Citation: Vazquez-Torres A, Fang F. 2000. Mechanisms of Resistance to NO-Related Antibacterial Activity, p 131-142. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch9
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