produced by the action of flavoproteins, Fe/S proteins, and
quinones during the electron transfer in the respiratory
chain. These compounds are the most stable of all the toxic
forms of oxygen and thus their time life is longer. They can
move from one cell to another, resulting in the oxidative
destruction of lipids. They are responsible for the sensitivity
to oxygen of strict anaerobic bacteria and archaea.
Hydrogen peroxide is stable too. It is formed by respiration at flavoproteins among aerobic organisms and
microorganisms.
The hydroxyl radical is the most reactive and least stable
of all forms of oxygen. It is the most oxidizing agent that can
oxidize and destroy all cell compounds (macromolecules).
It is formed during aerobic respiration, but also by ionizing
radiation (destroying effect of radiation by destructive
superoxydation).
Eukaryotes have also developed a response when they get
in contact with the bacteria that involve reactive species of
oxygen. They enzymes (NADPH oxidase, polyamine oxidase, peroxidases) can produce either peroxide or superoxide ions in what is called the oxidative burst (Bolwell 1996).
This is why pathogenic or symbiotic microorganisms must
be able to manage such a rapid increase in oxidative ion
concentration.
9.6.2.1 Proteins Induced by Oxidative Stress
At least 30 proteins are induced during a hydrogen peroxide
stress in response to increasing H 2 O 2 . The stimulus for
induction is still unknown. In E. coli, 8 proteins are necessary and are regulated by the regulon oxyR. The most important of these are catalases and peroxidases which can destroy
the molecule of H 2 O 2 according to the following equations:
Catalase : H 2 O 2 þ H 2 O 2 ! 2 H 2 O þ O 2
NADH‐dependent peroxidase : H 2 O 2 þ NADH þ H
þ ! 2 H 2 O þ NAD
þ
The oxyR gene encodes a protein which acts at oxyR
transcription interacting with RNA polymerase for transcription of defense enzymes. When the level of superoxide anion
(O 2
À ) is high, bacteria respond by using a different stimulon.
More than 30 proteins are also produced through the action
of gene regulators soxR and soxS. At least six proteins are
known and among them the superoxide dismutase which
converts superoxide to ion peroxide:
O
À
2 þ O
À
2 þ 2 H
þ
! H 2 O 2 þ O 2
The production of hydrogen peroxide leads then to the
induction of enzymes of the peroxide regulon. The mechanism
that allows the activation of the transcription of genes involved
in the synthesis of two proteins SoxR and SoxS is little known.
These proteins possess four cysteines in the carboxyl terminal
region, that probably bind to metal. The state of the redox
metal could act as a signal for transcription.
The presence of hydrogen peroxide in the cytoplasm is
already a significant cellular stress, but the presence of iron
(II) will exacerbate the situation by generating hydroxyl ions
in the so-called Fenton reaction which includes two distinct
reactions:
Fe
2þ
þ H 2 O 2 ! Fe
3þ
þ OH
þ OH
À
Fe
3þ
þ H 2 O 2 ! Fe
2þ
þ O Á OH þ H
þ
Iron is therefore a catalyst, and the produced highly
reactive ions will oxidize a wide range of compounds including lipids, DNA, and proteins. In several bacteria, especially
Actinobacteria, the regulator Fur is involved in the response
to oxidative stress, by the detection of ferric ions, potential
generators of Fenton reaction.
9.6.2.2 Responses to Oxidative Stress
During oxidative stress, the cellular responses and defenses
are of two kinds: preventive defenses and remedial defenses.
The preventive defenses can destroy the toxic oxygen species and result in the direct production of detoxification
enzymes: catalase, peroxidase, and superoxide dismutase
according to the toxic form involved. The remedial defenses
help to repair the damages caused by reactive forms of
oxygen such as by inducing the production of glutathione
reductase that lowers glutathione oxide and reduce intracellular redox potential. There is also a significant production
of glucose 6-phosphate dehydrogenase which allows the
synthesis of NADPH needed for glutathione reductase and
other reductases used to repair different enzymes damaged
by oxidation. If nucleic acids are also damaged, there may be
a stimulation of the production of endonuclease IV to repair
the DNA oxide, for example. Further damage can occur on
oxidized membranes which require also the presence of
reductases for repair.
In eukaryotes adapted to living conditions in the presence
of oxygen, different enzymatic equipments for preventive
and remedial defenses are present.
In prokaryotes (bacteria and archaea), the responses to
oxidative stress will vary according to the enzyme setup
present. Thus, four different behaviors in the presence of
oxygen may exist (Fig. 9.22):
(i) The bacterium is strictly aerobic*: it realizes aerobic
respiration (cf. Sect. 3.3.2) and therefore possesses the
systems of detoxification of toxic forms of oxygen.
This bacterium cannot live without oxygen.
(ii) The bacterium is facultatively anaerobic: it lives by
aerobic respiration and therefore possesses the systems
necessary to cope with oxidative stress, but it can also
live in the absence of oxygen by fermentation or
anaerobic respiration. Enzymes involved in fermentation or anaerobic respirations are derepressed and/or
induced and active in the absence of oxygen. The bacterium can also be air tolerant, that is to say, it can live in
328
P. Normand et al.
quinones during the electron transfer in the respiratory
chain. These compounds are the most stable of all the toxic
forms of oxygen and thus their time life is longer. They can
move from one cell to another, resulting in the oxidative
destruction of lipids. They are responsible for the sensitivity
to oxygen of strict anaerobic bacteria and archaea.
Hydrogen peroxide is stable too. It is formed by respiration at flavoproteins among aerobic organisms and
microorganisms.
The hydroxyl radical is the most reactive and least stable
of all forms of oxygen. It is the most oxidizing agent that can
oxidize and destroy all cell compounds (macromolecules).
It is formed during aerobic respiration, but also by ionizing
radiation (destroying effect of radiation by destructive
superoxydation).
Eukaryotes have also developed a response when they get
in contact with the bacteria that involve reactive species of
oxygen. They enzymes (NADPH oxidase, polyamine oxidase, peroxidases) can produce either peroxide or superoxide ions in what is called the oxidative burst (Bolwell 1996).
This is why pathogenic or symbiotic microorganisms must
be able to manage such a rapid increase in oxidative ion
concentration.
9.6.2.1 Proteins Induced by Oxidative Stress
At least 30 proteins are induced during a hydrogen peroxide
stress in response to increasing H 2 O 2 . The stimulus for
induction is still unknown. In E. coli, 8 proteins are necessary and are regulated by the regulon oxyR. The most important of these are catalases and peroxidases which can destroy
the molecule of H 2 O 2 according to the following equations:
Catalase : H 2 O 2 þ H 2 O 2 ! 2 H 2 O þ O 2
NADH‐dependent peroxidase : H 2 O 2 þ NADH þ H
þ ! 2 H 2 O þ NAD
þ
The oxyR gene encodes a protein which acts at oxyR
transcription interacting with RNA polymerase for transcription of defense enzymes. When the level of superoxide anion
(O 2
À ) is high, bacteria respond by using a different stimulon.
More than 30 proteins are also produced through the action
of gene regulators soxR and soxS. At least six proteins are
known and among them the superoxide dismutase which
converts superoxide to ion peroxide:
O
À
2 þ O
À
2 þ 2 H
þ
! H 2 O 2 þ O 2
The production of hydrogen peroxide leads then to the
induction of enzymes of the peroxide regulon. The mechanism
that allows the activation of the transcription of genes involved
in the synthesis of two proteins SoxR and SoxS is little known.
These proteins possess four cysteines in the carboxyl terminal
region, that probably bind to metal. The state of the redox
metal could act as a signal for transcription.
The presence of hydrogen peroxide in the cytoplasm is
already a significant cellular stress, but the presence of iron
(II) will exacerbate the situation by generating hydroxyl ions
in the so-called Fenton reaction which includes two distinct
reactions:
Fe
2þ
þ H 2 O 2 ! Fe
3þ
þ OH
þ OH
À
Fe
3þ
þ H 2 O 2 ! Fe
2þ
þ O Á OH þ H
þ
Iron is therefore a catalyst, and the produced highly
reactive ions will oxidize a wide range of compounds including lipids, DNA, and proteins. In several bacteria, especially
Actinobacteria, the regulator Fur is involved in the response
to oxidative stress, by the detection of ferric ions, potential
generators of Fenton reaction.
9.6.2.2 Responses to Oxidative Stress
During oxidative stress, the cellular responses and defenses
are of two kinds: preventive defenses and remedial defenses.
The preventive defenses can destroy the toxic oxygen species and result in the direct production of detoxification
enzymes: catalase, peroxidase, and superoxide dismutase
according to the toxic form involved. The remedial defenses
help to repair the damages caused by reactive forms of
oxygen such as by inducing the production of glutathione
reductase that lowers glutathione oxide and reduce intracellular redox potential. There is also a significant production
of glucose 6-phosphate dehydrogenase which allows the
synthesis of NADPH needed for glutathione reductase and
other reductases used to repair different enzymes damaged
by oxidation. If nucleic acids are also damaged, there may be
a stimulation of the production of endonuclease IV to repair
the DNA oxide, for example. Further damage can occur on
oxidized membranes which require also the presence of
reductases for repair.
In eukaryotes adapted to living conditions in the presence
of oxygen, different enzymatic equipments for preventive
and remedial defenses are present.
In prokaryotes (bacteria and archaea), the responses to
oxidative stress will vary according to the enzyme setup
present. Thus, four different behaviors in the presence of
oxygen may exist (Fig. 9.22):
(i) The bacterium is strictly aerobic*: it realizes aerobic
respiration (cf. Sect. 3.3.2) and therefore possesses the
systems of detoxification of toxic forms of oxygen.
This bacterium cannot live without oxygen.
(ii) The bacterium is facultatively anaerobic: it lives by
aerobic respiration and therefore possesses the systems
necessary to cope with oxidative stress, but it can also
live in the absence of oxygen by fermentation or
anaerobic respiration. Enzymes involved in fermentation or anaerobic respirations are derepressed and/or
induced and active in the absence of oxygen. The bacterium can also be air tolerant, that is to say, it can live in
328
P. Normand et al.