The mechanism of action of the arylomycin antibiotics and the effects of signal peptidase I inhibition
P.A. Smith, F.E. Romesberg, Antimicrob. Agents Chemother. (2012) 56:5054-5060.
We examine arylomycin activity as a function of concentration, bacterial cell density, target expression levels, and bacterial growth phase. We find that the activity of the arylomycins results from an insufficient flux of proteins through the secretion pathway and the resulting mislocalization of proteins. We also demonstrate that SPase inhibition results in synergistic sensitivity when combined with an aminoglycoside.