Multidrug-Resistant Acinetobacter baumannii Chloramphenicol Resistance Requires an Inner Membrane Permease.
Multidrug-Resistant Acinetobacter baumannii Chloramphenicol Resistance Requires an Inner Membrane Permease.
复制标题
DOI：
10.1128/aac.00513-18
复制
发表时间：
2018-08-01
影响因子：
4.9
通讯作者：
Miller, Samuel I
中科院分区：
文献类型：
--
作者：
Karalewitz, Andrew P-A;Miller, Samuel I
鲍曼不动杆菌是一种革兰氏阴性微生物，是医院获得性多重耐药（MDR）感染的原因。A.与许多其它革兰氏阴性病原体相比，鲍曼不动杆菌具有独特的细胞表面，因为它可以在没有脂多糖（LPS）的情况下存活，并且它在外膜中具有高含量的心磷脂。因此，为了更好地了解MDR A的细胞膜和机制。在鲍曼不动杆菌中，我们筛选了转座子文库中具有缺陷性渗透屏障功能的突变体，所述缺陷性渗透屏障功能定义为排除磷酸酶显色底物5-溴-4-氯-3-吲哚基磷酸（XP）的能力的缺陷。我们鉴定了ABUW_0982基因中的多个突变体，预测其编码广泛存在于A.对核糖体靶向抗生素氯霉素（CHL）敏感性增加的鲍曼不动杆菌分离株。与其他已知的氯霉素酰基转移酶基因相比，我们发现ABUW_0982是A.鲍曼不动杆菌菌株5075（Ab 5075）是导致人类严重MDR感染的重要分离株。最后，在CHL敏感大肠杆菌中测量氯霉素外排和ABUW_0982表达的研究支持以下结论：ABUW_0982编码对包括CHL在内的小疏水分子具有特异性的单组分外排蛋白。
Acinetobacter baumannii is a Gram-negative organism that is a cause of hospital-acquired multidrug-resistant (MDR) infections. A. baumannii has a unique cell surface compared to those of many other Gram-negative pathogens in that it can live without lipopolysaccharide (LPS) and it has a high content of cardiolipin in the outer membrane. Therefore, to better understand the cell envelope and mechanisms of MDR A. baumannii, we screened a transposon library for mutants with defective permeability barrier function, defined as a deficiency in the ability to exclude the phosphatase chromogenic substrate 5-bromo-4-chloro-3-indolylphosphate (XP). We identified multiple mutants with mutations in the ABUW_0982 gene, predicted to encode a permease broadly present in A. baumannii isolates with increased susceptibility to the ribosome-targeting antibiotic chloramphenicol (CHL). Moreover, compared to other known CHL resistance genes, such as chloramphenicol acyltransferase genes, we found that ABUW_0982 is the primary determinant of intrinsic CHL resistance in A. baumannii strain 5075 (Ab5075), an important isolate responsible for severe MDR infections in humans. Finally, studies measuring the efflux of chloramphenicol and expression of ABUW_0982 in CHL-susceptible Escherichia coli support the conclusion that ABUW_0982 encodes a single-component efflux protein with specificity for small, hydrophobic molecules, including CHL.