The Fumarate Reductase of <italic toggle="yes">Bacteroides thetaiotaomicron</italic>, unlike That of <italic toggle="yes">Escherichia coli</italic>, Is Configured so that It Does Not Generate Reactive Oxygen Species

ABSTRACT The impact of oxidative stress upon organismal fitness is most apparent in the phenomenon of obligate anaerobiosis. The root cause may be multifaceted, but the intracellular generation of reactive oxygen species (ROS) likely plays a key role. ROS are formed when redox enzymes accidentally t...

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Autores principales:	Zheng Lu, James A. Imlay
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/40dcb61758684409ad0ef3cd586ed274
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spelling	oai:doaj.org-article:40dcb61758684409ad0ef3cd586ed2742021-11-15T15:51:06ZThe Fumarate Reductase of <italic toggle="yes">Bacteroides thetaiotaomicron</italic>, unlike That of <italic toggle="yes">Escherichia coli</italic>, Is Configured so that It Does Not Generate Reactive Oxygen Species10.1128/mBio.01873-162150-7511https://doaj.org/article/40dcb61758684409ad0ef3cd586ed2742017-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01873-16https://doaj.org/toc/2150-7511ABSTRACT The impact of oxidative stress upon organismal fitness is most apparent in the phenomenon of obligate anaerobiosis. The root cause may be multifaceted, but the intracellular generation of reactive oxygen species (ROS) likely plays a key role. ROS are formed when redox enzymes accidentally transfer electrons to oxygen rather than to their physiological substrates. In this study, we confirm that the predominant intestinal anaerobe Bacteroides thetaiotaomicron generates intracellular ROS at a very high rate when it is aerated. Fumarate reductase (Frd) is a prominent enzyme in the anaerobic metabolism of many bacteria, including B. thetaiotaomicron, and prior studies of Escherichia coli Frd showed that the enzyme is unusually prone to ROS generation. Surprisingly, in this study biochemical analysis demonstrated that the B. thetaiotaomicron Frd does not react with oxygen at all: neither superoxide nor hydrogen peroxide is formed. Subunit-swapping experiments indicated that this difference does not derive from the flavoprotein subunit at which ROS normally arise. Experiments with the related enzyme succinate dehydrogenase discouraged the hypothesis that heme moieties are responsible. Thus, resistance to oxidation may reflect a shift of electron density away from the flavin moiety toward the iron-sulfur clusters. This study shows that the autoxidizability of a redox enzyme can be suppressed by subtle modifications that do not compromise its physiological function. One implication is that selective pressures might enhance the oxygen tolerance of an organism by manipulating the electronic properties of its redox enzymes so they do not generate ROS. IMPORTANCE Whether in sediments or pathogenic biofilms, the structures of microbial communities are configured around the sensitivities of their members to oxygen. Oxygen triggers the intracellular formation of reactive oxygen species (ROS), and the sensitivity of a microbe to oxygen likely depends upon the rates at which ROS are formed inside it. This study supports that idea, as an obligate anaerobe was confirmed to generate ROS very rapidly upon aeration. However, the suspected source of the ROS was disproven, as the fumarate reductase of the anaerobe did not display the high oxidation rate of its E. coli homologue. Evidently, adjustments in its electronic structure can suppress the tendency of an enzyme to generate ROS. Importantly, this outcome suggests that evolutionary pressure may succeed in modifying redox enzymes and thereby diminishing the stress that an organism experiences in oxic environments. The actual source of ROS in the anaerobe remains to be discovered.Zheng LuJames A. ImlayAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 1 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Zheng Lu James A. Imlay The Fumarate Reductase of <italic toggle="yes">Bacteroides thetaiotaomicron</italic>, unlike That of <italic toggle="yes">Escherichia coli</italic>, Is Configured so that It Does Not Generate Reactive Oxygen Species
description	ABSTRACT The impact of oxidative stress upon organismal fitness is most apparent in the phenomenon of obligate anaerobiosis. The root cause may be multifaceted, but the intracellular generation of reactive oxygen species (ROS) likely plays a key role. ROS are formed when redox enzymes accidentally transfer electrons to oxygen rather than to their physiological substrates. In this study, we confirm that the predominant intestinal anaerobe Bacteroides thetaiotaomicron generates intracellular ROS at a very high rate when it is aerated. Fumarate reductase (Frd) is a prominent enzyme in the anaerobic metabolism of many bacteria, including B. thetaiotaomicron, and prior studies of Escherichia coli Frd showed that the enzyme is unusually prone to ROS generation. Surprisingly, in this study biochemical analysis demonstrated that the B. thetaiotaomicron Frd does not react with oxygen at all: neither superoxide nor hydrogen peroxide is formed. Subunit-swapping experiments indicated that this difference does not derive from the flavoprotein subunit at which ROS normally arise. Experiments with the related enzyme succinate dehydrogenase discouraged the hypothesis that heme moieties are responsible. Thus, resistance to oxidation may reflect a shift of electron density away from the flavin moiety toward the iron-sulfur clusters. This study shows that the autoxidizability of a redox enzyme can be suppressed by subtle modifications that do not compromise its physiological function. One implication is that selective pressures might enhance the oxygen tolerance of an organism by manipulating the electronic properties of its redox enzymes so they do not generate ROS. IMPORTANCE Whether in sediments or pathogenic biofilms, the structures of microbial communities are configured around the sensitivities of their members to oxygen. Oxygen triggers the intracellular formation of reactive oxygen species (ROS), and the sensitivity of a microbe to oxygen likely depends upon the rates at which ROS are formed inside it. This study supports that idea, as an obligate anaerobe was confirmed to generate ROS very rapidly upon aeration. However, the suspected source of the ROS was disproven, as the fumarate reductase of the anaerobe did not display the high oxidation rate of its E. coli homologue. Evidently, adjustments in its electronic structure can suppress the tendency of an enzyme to generate ROS. Importantly, this outcome suggests that evolutionary pressure may succeed in modifying redox enzymes and thereby diminishing the stress that an organism experiences in oxic environments. The actual source of ROS in the anaerobe remains to be discovered.
format	article
author	Zheng Lu James A. Imlay
author_facet	Zheng Lu James A. Imlay
author_sort	Zheng Lu
title	The Fumarate Reductase of <italic toggle="yes">Bacteroides thetaiotaomicron</italic>, unlike That of <italic toggle="yes">Escherichia coli</italic>, Is Configured so that It Does Not Generate Reactive Oxygen Species
title_short	The Fumarate Reductase of <italic toggle="yes">Bacteroides thetaiotaomicron</italic>, unlike That of <italic toggle="yes">Escherichia coli</italic>, Is Configured so that It Does Not Generate Reactive Oxygen Species
title_full	The Fumarate Reductase of <italic toggle="yes">Bacteroides thetaiotaomicron</italic>, unlike That of <italic toggle="yes">Escherichia coli</italic>, Is Configured so that It Does Not Generate Reactive Oxygen Species
title_fullStr	The Fumarate Reductase of <italic toggle="yes">Bacteroides thetaiotaomicron</italic>, unlike That of <italic toggle="yes">Escherichia coli</italic>, Is Configured so that It Does Not Generate Reactive Oxygen Species
title_full_unstemmed	The Fumarate Reductase of <italic toggle="yes">Bacteroides thetaiotaomicron</italic>, unlike That of <italic toggle="yes">Escherichia coli</italic>, Is Configured so that It Does Not Generate Reactive Oxygen Species
title_sort	fumarate reductase of <italic toggle="yes">bacteroides thetaiotaomicron</italic>, unlike that of <italic toggle="yes">escherichia coli</italic>, is configured so that it does not generate reactive oxygen species
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/40dcb61758684409ad0ef3cd586ed274
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The Fumarate Reductase of <italic toggle="yes">Bacteroides thetaiotaomicron</italic>, unlike That of <italic toggle="yes">Escherichia coli</italic>, Is Configured so that It Does Not Generate Reactive Oxygen Species

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