Teicoplanin Stress-Selected Mutations Increasing ς B Activity in Staphylococcus aureus

Abstract

ABSTRACT A natural rsbU mutant of Staphylococcus aureus, unable to activate the alternative transcription factor ς B via the RsbU pathway and therefore forming unpigmented colonies, produced first-step teicoplanin-resistant mutants upon selection for growth in the presence of teicoplanin, of which the majority were of an intense orange color. By using an asp23 promoter-luciferase fusion as an indicator, the pigmented mutants were shown to express increased ς B activity. Increased ς B activity was associated with point mutations in rsbW, releasing ς B from sequestration by the anti-sigma factor RsbW, or to promoter mutations increasing the ς B /RsbW ratio. Genetic manipulations involving the sigB operon suggested that the mutations within the operon were associated with the increase in teicoplanin resistance. The upregulation of ς B suggests that a ς B -controlled gene(s) is directly or indirectly involved in the development of teicoplanin resistance in S. aureus . Carotenoids do not contribute to teicoplanin resistance, since inactivation of the dehydrosqualene synthase gene crtM abolished pigment formation without affecting teicoplanin resistance. The relevant ς B -controlled target genes involved in teicoplanin resistance remain to be identified.