Growth inhibition of hopanoid synthesizing bacteria by squalene cyclase inhibitors

Abstract

2,3-Dihydro-2-azasqualene, its N-oxide and its N,N-diethyl analogue, as well as 2,3-dihydro-2,3-iminosqualene are potent inhibitors of the squalene to hopanoid (diplotene and diplopterol) cyclases in cell-free systems from Acetobacter pasteurianus ssp pasteurianus, Methylobacterium organophilum and Zymomonas mobilis. The inhibitory concentration giving 50% inhibition at a 120 μM squalene concentration was determined in each cases. The growth of hopanoid producing prokaryotes (with the exception of Acetobacter pasteurianus ssp pasteurianus and Pseudomonas syringae probably capable of degrading the drugs) was inhibited by these squalene analogues at concentrations in the μM range, whereas the growth of hopanoid non-producers was not affected at the highest tested concentration (200 μM). Thus hopanoids which have been shown to possess similar properties to those of sterols in membrane reinforcement are probably essential for the cells producing them. Furthermore, all tested hopanoid producers are very sensitive to trimethyloctadecyl ammonium bromide which does not inhibit the squalene to hopane cyclases at a 50 μM concentration, and do not grow after 24 h in its presence at a 1 μM minimal inhibitory concentration. Growth of hopanoid non-producers was however not affected by this ammonium salt (highest tested concentration: 200 μM). The mode of action of this cationic detergent is still unknown, but might be related to specific desorganization of hopanoid containing membranes.