Antitumor drugs inhibit the growth of halophilic archaebacteria

Abstract

Permeability mutants of Escherichia coli have been used to prescreen antitumor drugs. However, most compounds active against eucaryotic proteins have no effect on isofunctional proteins of eubacteria. In contrast, we show that growth of halophilic archaebacteria. procaryotes as distantly related to eubacteria as to eucaryotes, is inhibited by several drugs known to interact with tubulin, actomyosin and DNA topoisomerase II of eucaryotes. Actually, different types of evidence indicate the presence of analogous proteins in halophilic archaebacteria: (a) a yeast actin probe hybridizes with DNA restriction digests of Halobacterium halobium; (b) antibodies against tubulin and actin from chicken react in a crude extract of H. halobium with polypeptides having Mr of 55000 and 80000, respectively; (c) the epipodophyllotoxin VP16, a eucaryotic DNA topoisomerase II inhibitor, induces DNA strand breaks with DNA-protein covalent linkage in H. halobium as in eucaryotes. Besides the evolutionary implications, these data indicate that halophilic archaebacteria can be used to prescreen antitumor drugs active on eucaryotic proteins.