Visalli Melissa A, Murphy Ellen, Projan Steven J, Bradford Patricia A
Wyeth Research, Pearl River, New York, USA.
Antimicrob Agents Chemother. 2003 Feb;47(2):665-9. doi: 10.1128/AAC.47.2.665-669.2003.
Tigecycline has good broad-spectrum activity against many gram-positive and gram-negative pathogens with the notable exception of the PROTEEAE: A study was performed to identify the mechanism responsible for the reduced susceptibility to tigecycline in Proteus mirabilis. Two independent transposon insertion mutants of P. mirabilis that had 16-fold-increased susceptibility to tigecycline were mapped to the acrB gene homolog of the Escherichia coli AcrRAB efflux system. Wild-type levels of decreased susceptibility to tigecycline were restored to the insertion mutants by complementation with a clone containing a PCR-derived fragment from the parental wild-type acrRAB efflux gene cluster. The AcrAB transport system appears to be associated with the intrinsic reduced susceptibility to tigecycline in P. mirabilis.
替加环素对许多革兰氏阳性和革兰氏阴性病原体具有良好的广谱活性,但奇异变形杆菌属是个明显的例外:开展了一项研究以确定奇异变形杆菌对替加环素敏感性降低的机制。两个对替加环素敏感性提高了16倍的奇异变形杆菌独立转座子插入突变体被定位到大肠杆菌AcrRAB外排系统的acrB基因同源物上。通过用包含来自亲本野生型acrRAB外排基因簇的PCR衍生片段的克隆进行互补,使插入突变体恢复到对替加环素敏感性降低的野生型水平。AcrAB转运系统似乎与奇异变形杆菌对替加环素的固有敏感性降低有关。