INDUCIBLE NORA-MEDIATED MULTIDRUG-RESISTANCE IN STAPHYLOCOCCUS-AUREUS
INDUCIBLE NORA-MEDIATED MULTIDRUG-RESISTANCE IN STAPHYLOCOCCUS-AUREUS
复制标题
DOI：
10.1128/aac.39.12.2650
复制
发表时间：
1995-12-01
影响因子：
4.9
通讯作者：
SEO, SM
中科院分区：
文献类型：
--
作者：
KAATZ, GW;SEO, SM
金黄色葡萄球菌的NorA蛋白介导亲水性氟喹诺酮类药物从细胞中主动外排，使生物体产生低水平的耐药性。该蛋白还能够运输额外的结构多样化的化合物，表明它具有广泛的底物特异性。被认为是具有这种变化的菌株抵抗氟喹诺酮类药物的机制。金黄色葡萄球菌SA-1199及其在体内选择的衍生物SA-1199B分别是氟喹诺酮敏感株和耐药株；SA-1199B通过诺拉介导的机制对亲水性氟喹诺酮类药物产生组成性耐药，SA-1199-3是SA-1199的体外衍生物，其中诺拉介导的多药耐药可诱导表达。与首次暴露于亚抑制浓度的NorA底物的生物体相比，将SA-1199-3预先暴露于这种化合物，然后在该底物存在的情况下生长，可消除在开始对数生长之前发生的2至6小时的生物体杀伤。这种预先暴露也会导致与norA探针杂交的RNA转录物的急剧增加，SA-1199和SA-1199B预先暴露于这种底物会导致这些转录物的少量增加或没有增加，在norA基因或侧翼DNA中SA-1199和SA-1199-3之间没有发现序列差异，似乎SA-1199-3中nor a的调节可能受到染色体norA区域外的一个或多个遗传位点的影响。不同于SA-1199和SA-1199B。
The NorA protein of Staphylococcus aureus mediates the active efflux of hydrophilic fluoroquinolones from the cell, conferring low-level resistance upon the organism, This protein also is capable of transporting additional structurally diverse compounds, indicating that it has a broad substrate specificity, Increased transcription of the norA gene, leading to a greater quantity of the NorA protein within the cytoplasmic membrane, is felt to be the mechanism by which strains possessing such changes resist fluoroquinolones. S. aureus SA-1199 and its in vivo-selected derivative SA-1199B are fluoroquinolone-susceptible and -resistant isolates, respectively; SA-1199B resists hydrophilic fluoroquinolones via a NorA-mediated mechanism in a constitutive manner, SA-1199-3 is an in vitro-produced derivative of SA-1199 in which NorA-mediated multidrug resistance is expressed inducibly. Compared with organisms exposed to subinhibitory concentrations of a NorA substrate for the first time, preexposure of SA-1199-3 to such a compound followed by growth in the presence of that substrate results in the elimination of a 2- to 6-h period of organism killing that occurs prior to the onset of logarithmic growth, The uptake of radiolabeled fluoroquinolone is markedly reduced by preexposure of SA-1199-3 to NorA substrates; such prior exposure also results in a dramatic increase in RNA transcripts that hybridize with a norA probe, Preexposure of SA-1199 and SA-1199B to such substrates results in small increases or no increases in these transcripts, No sequence differences between SA-1199 and SA-1199-3 within the norA gene or flanking DNA were found, It appears likely that the regulation of nor A in SA-1199-3, which mag be effected by one or more genetic loci outside the norA region of the chromosome, differs from that of SA-1199 and SA-1199B.