Bactericidal activity and bacteriostasis mechanisms of action

Molecular oxygen is relatively inert but can react with organic molecules, inducing the production of highly reactive intermediates: free radicals or reactive oxygen species (ROS)2930. The development and accumulation of free radicals account for the bactericidal and bacteriostatic effects of an increase in pressure of oxygen. It is generally agreed that bacteria with no defence mechanisms against free radicals are more susceptible to an increase in pressure of oxygen5,16.

Free radicals are a type of molecule with one or more free electrons. Oxygen molecules include two free electrons on two different orbitals but spinning in parallel. To react with other molecules and accept electrons (oxidation), these must spin inversely - this is why molecular oxygen is not very reactive. But when oxygen molecules accept just one electron, an oxygen superoxide radical (O2") is formed30:

Superoxide radicals are mostly produced in the mitochondria during redox reactions. The quantity of O2* produced increases in proportion to the concentration in oxygen. In aqueous media, O2* turns into hydrogen peroxide (H2O2) by a dismutation reaction:

2O2' + 2H+ ^ H2O2 + O2 Hydrogen peroxide is not considered a free radical because it does not have any free electron. However, hydrogen peroxide passes readily through membranes while radicals like O2" are charged and therefore do not. The capacity of hydrogen peroxide for deleterious effects is therefore due to its great diffusivity. It becomes reactive when in contact with certain metal ions such as iron or copper. This reaction causes a highly reactive hydroxyl radical (OH") to be produced (Fenton's reaction):

Fe2+ + H2O2 ^ Fe3+ + OH" + OH Neither the superoxide radical anion nor the hydrogen peroxide are particularly cytotoxic per se, but as both can generate hydroxyl radicals they are potentially highly dangerous. The hydroxyl radical reacts very swiftly with many molecules such as DNA, proteins and carbohydrates. It also destroys membrane lipids in a lipid peroxydation process (chain reaction). Free radicals can encourage the production of secondary messengers such as diacylglycerol or phosphatidic acid by its activity on cell membranes.

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