Statins inhibit in vitro virulence phenotypes of Pseudomonas aeruginosa

Statins are a family of drugs that lower cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl-CoA-reductase, a rate-limiting enzyme in the human mevalonate pathway of which cholesterol is the biosynthetic end product.1Statins also have a range of cholesterol-independent effects, including anti-inflammatory functions and antimicrobial activity. These pleiotropic effects are thought to account for the improved survival observed in statin-treated patients suffering from severe bacterial infections, such as sepsis and pneumonia.2, 3, 4 In order to identify the mechanism involved in the protective effects of statins against infection, research studies focused on the direct effect of statins on bacteria. These studies suggest that statins have bacteriostatic effects on the in vitro growth of clinically important bacterial species, including Staphylococcus aureus and Enterococci,5 Streptococcus pneumoniae and Moraxella catarrhalis,6 and Escherichia coli andPseudomonas aeruginosa.7 However, the concentrations used in these in vitro studies exceed the concentration detected in human serum during statin therapy,6 suggesting the in vitro bacteriostatic effects of statins are not likely to account for the beneficial outcome of patients suffering from severe bacterial infections.