In Vitro Activities of Arylomycin Natural-Product Antibiotics against Staphylococcus epidermidis and Other Coagulase-Negative Staphylococci

Abstract

ABSTRACT The arylomycins are a class of natural-product antibiotics that act via the inhibition of type I signal peptidase (SPase), and we have found in diverse bacteria that their activity is limited by the presence of a resistance-conferring Pro residue in SPase that reduces inhibitor binding. We have also demonstrated that Staphylococcus epidermidis , which lacks this Pro residue, is extremely susceptible to the arylomycins. Here, to further explore the potential utility of the arylomycins, we report an analysis of the activity of a synthetic arylomycin derivative, arylomycin C 16 , against clinical isolates of S. epidermidis and other coagulase-negative staphylococci (CoNS) from distinct geographical locations. Against many important species of CoNS, including S. epidermidis , S. haemolyticus , S. lugdunensis , and S. hominis , we find that arylomycin C 16 exhibits activity equal to or greater than that of vancomycin, the antibiotic most commonly used to treat CoNS infections. While the susceptibility was generally correlated with the absence of the previously identified Pro residue, several cases were identified where additional factors also appear to contribute.