Section Reviews; Anti-infectives: Section Review Anti-infectives: Natural mediators of host-defence: The role of H₂O₂ in the regulation of bacteriostasis

Abstract

Host-defence against many different pathogenic microorganisms in higher life forms is mediated in part by the production of reactive oxygen species (ROS) generated by a variety of different cellular mechanisms. Since ROS are highly toxic to all living cells, it is important to understand how ROS are used specifically by higher organisms to eliminate pathogens, without causing undue tissue damage to the host. Total elimination of the pathogen clearly involves complete killing, and is generally referred to in this review in general terms as a ‘bactericidal’ process (although not all pathogens eliminated by these mechanisms are necessarily bacteria). However, killing of microorganisms by mechanisms involving ROS must be carefully compartmentalised to avoid injury to the host. Other mechanisms of controlling pathogens may involve processes that inhibit the growth of the pathogen. This effect on invading pathogens is referred to as ‘bacteriostasis’, (again, this process is not necessarily limited to just bacteria). In this review, some of these issues will be reviewed, with special reference to H₂O₂ produced in the extracellular fluid. This oxidant may have a special role in host defence, in that it inhibits cell division at relatively low concentrations (< 50 μM), without causing cellular toxicity. The experimental evidence that this mechanism plays a central role in host defence will be reviewed.