Biology Reference
In-Depth Information
The biological targets for ROS are DNA, RNA, proteins, and lipids. In
bacteria, it has been shown that the most damaging effects of ROS result
from its interactions with reduced iron (and to a lesser extent, copper) centers
in proteins. These initial oxidation reactions cause the release of Fe 3 + from
Fe-S proteins contributing to the “free” Fe pool. This Fe can then react with
H 2 O 2 and generate OH · through the Fenton reaction (2) .OH · reacts with
most biomolecules and because it is so reactive, will react with them within
a cell at diffusion-limited rates. The average diffusion distance is only a few
nanometers, and thus, its effect on any given biomolecule will depend largely
upon proximity to the target. Because Fe can localize along the phosphodiester
backbone of nucleic acid, DNA is a major target of ROS. Active species can
attack both the base and sugar moieties producing single- and double-strand
breaks in the backbone and crosslinks to other molecules. As some of the base
damage can result in miscoding, lesions formed by endogenous oxidants may
be a significant or even preponderant source of spontaneous mutagenesis in
aerobically growing cells. Because the reaction requires Fe 3 + /Cu 3 + , the amount
of DNA damage that results from Fenton chemistry depends upon the metal
metabolism of the bacteria. In the case of Borrelia burgdorferi , intracellular Fe
concentrations are estimated to be <10 atoms per cell (3) . At those levels, it is
unlikely that B. burgdorferi DNA is a target for ROS.
Lipids are a major target during oxidative stress in eukaryotes. Free radicals
can attack polyunsaturated fatty acids in membranes and initiate lipid peroxi-
dation. A primary effect of this is a decrease in membrane fluidity that affects
the properties of the membrane and alters the function of membrane-associated
proteins. Once lipid peroxides have formed, they react with adjacent polyunsat-
urated lipids causing an amplification of the damage. Lipid peroxides degrade
into a variety of products, including aldehydes, which can subsequently damage
membrane proteins and affect membrane fluidity. Unlike reactive free radicals,
aldehydes are rather long-lived and can therefore diffuse from the site of origin
and attack targets that are distant from the initial reaction. Until recently, it was
assumed that bacterial lipids were not subject to oxidative damage observed
in eukaryotic cells. Only certain polyunsaturated lipids, such as linoleic and
linolenic acid, are subject to attack (4) , and it is clear that most bacteria do
not synthesize or contain these types of lipids in their membranes. Interest-
ingly, linoleic acid and linolenic acid is incorporated into the membranes of
some pathogenic bacteria including B. burgdorferi (5,6) . As these bacteria
cannot synthesize their own lipids and must scavenge them, their membrane
composition often reflects the host's lipid profile or that of their growth
medium (7,8,9) . Approximately, 10% of B. burgdorferi's total lipid content
is linoleic acid, suggesting that their membranes could undergo peroxidation
when exposed to ROS.
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