Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Antimicrob Agents Chemother. 2011 Mar;55(3):1130-4. doi: 10.1128/AAC.01459-10. Epub 2010 Dec 28.
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 C₁₆, 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 C₁₆ 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.
芳基霉素是一类通过抑制 I 型信号肽酶 (SPase) 发挥作用的天然产物抗生素，我们在多种细菌中发现，其活性受到 SPase 中赋予抗性的 Pro 残基的限制，该残基降低了抑制剂的结合。我们还证明，缺乏这种 Pro 残基的表皮葡萄球菌对芳基霉素极其敏感。在这里，为了进一步探索芳基霉素的潜在用途，我们报告了一种合成芳基霉素衍生物芳基霉素 C₁₆对来自不同地理位置的表皮葡萄球菌和其他凝固酶阴性葡萄球菌 (CoNS) 的临床分离株的活性分析。针对许多重要的 CoNS 物种，包括表皮葡萄球菌、溶血葡萄球菌、路邓葡萄球菌和人葡萄球菌，我们发现芳基霉素 C₁₆的活性与万古霉素相当或更高，万古霉素是最常用于治疗 CoNS 感染的抗生素。虽然敏感性通常与先前鉴定的 Pro 残基缺失相关，但也鉴定出了几个似乎还存在其他因素的情况。
