Intracellular Accumulation of Staphylopine Impairs the Fitness of Staphylococcus aureus cntE Mutant

: Staphylococcus aureus exports staphylopine (StP), a broad-spectrum metallophore, via the CntE efflux pump. Here, the mechanism of the fitness defect in the ΔcntE mutant under metal depletion was investigated. Deletion of the StP exporter CntE results in a substantial growth defect, and disrupting the StP biosynthesis gene cntL restores growth of the ΔcntE mutant in metal-depleted media. High-resolution mass spectrometry revealed cytoplasmic accumulation of StP and the absence of extracellular StP in the ΔcntE mutant. The fitness defect of the ΔcntE mutant in mouse subcutaneous abscesses is largely due to StP accumulation. Expression of StP biosynthesis genes are upregulated in the ΔcntE mutant under metal starvation induction. In conclusion, failure to efflux StP results in intracellular StP accumulation and substantially impairs the fitness of S. aureus.