Genetic Determinants Involved in the Susceptibility of Pseudomonas aeruginosa to β-Lactam Antibiotics
Genetic Determinants Involved in the Susceptibility of Pseudomonas aeruginosa to β-Lactam Antibiotics
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DOI：
10.1128/aac.00257-10
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发表时间：
2010-10-01
影响因子：
4.9
通讯作者：
Luis Martinez, Jose
中科院分区：
文献类型：
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作者：
Alvarez-Ortega, Carolina;Wiegand, Irith;Luis Martinez, Jose
铜绿假单胞菌对三种β-内酰胺类抗生素（即头孢他啶、亚胺培南和美罗培南）的耐药基因组通过筛选对这些抗生素敏感性增加或降低的突变体的综合PA 14突变体库来破译。通过Etest确认所有选定突变体的表型。在总共78个确认的突变体中，41个表现出降低的易感性表型，37个表现出超易感性（即，改变的内在耐药性）表型，其中6种突变体表现出混合表型，具体取决于抗生素。只有三个突变体表现出降低（PA 0908）或增加（glnK和ftsK）的敏感性，所有三种抗生素。总体而言，敏感性的突变体概况表明，尽管它们的结构相似，但三种抗生素的作用和耐药性机制不同。更详细的分析表明，新的和已知的β-内酰胺酶调控基因，可能参与屏障功能的基因，以及一系列的海藻酸盐生物合成的调节剂的重要作用。
The resistome of P. aeruginosa for three beta-lactam antibiotics, namely, ceftazidime, imipenem, and meropenem, was deciphered by screening a comprehensive PA14 mutant library for mutants with increased or reduced susceptibility to these antimicrobials. Confirmation of the phenotypes of all selected mutants was performed by Etest. Of the total of 78 confirmed mutants, 41 demonstrated a reduced susceptibility phenotype and 37 a supersusceptibility (i.e., altered intrinsic resistance) phenotype, with 6 mutants demonstrating a mixed phenotype, depending on the antibiotic. Only three mutants demonstrated reduced (PA0908) or increased (glnK and ftsK) susceptibility to all three antibiotics. Overall, the mutant profiles of susceptibility suggested distinct mechanisms of action and resistance for the three antibiotics despite their similar structures. More detailed analysis indicated important roles for novel and known beta-lactamase regulatory genes, for genes with likely involvement in barrier function, and for a range of regulators of alginate biosynthesis.