Inhibition of staphyloxanthin biosynthesis in Staphylococcus aureus by rhodomyrtone, a novel antibiotic candidate

Staphyloxanthin is the eponymous feature of the human pathogen Staphylococcus aureus, and the pigment promotes resistance to reactive oxygen species and host neutrophil-based killing. To probe the possible use of rhodomyrtone isolated from Rhodomyrtus tomentosa (Aiton) Hassk. leaves to inhibit pigment production in S. aureus, experiments were carried out to compare pigment production and the susceptibility of rhodomyrtone-treated S. aureus and untreated cells to oxidants in vitro. In addition, we observed the innate immune clearance of S. aureus after incubation with rhodomyrtone using an ex vivo assay system human whole-blood survival. The results indicated that rhodomyrtone-treated S. aureus exhibited reduced pigmentation, and that rhodomyrtone treatment led to a dose-dependent increase in the susceptibility of the pathogen to H2O2 and singlet oxygen killing. Consequently, the survival ability of the treated organisms decreased in freshly isolated human whole blood due to less carotenoid pigment to act as an antioxidant scavenger. Rhodomyrtone may be acting via effects on DnaK and/or sigma(B), resulting in many additional effects on bacterial virulence.