OUTER-MEMBRANE PERMEABILITY IN PSEUDOMONAS-AERUGINOSA - COMPARISON OF A WILD-TYPE WITH AN ANTIBIOTIC-SUPERSUSCEPTIBLE MUTANT

OUTER-MEMBRANE PERMEABILITY IN PSEUDOMONAS-AERUGINOSA - COMPARISON OF A WILD-TYPE WITH AN ANTIBIOTIC-SUPERSUSCEPTIBLE MUTANT
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DOI:
10.1128/aac.21.2.299
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发表时间:
1982-01-01
影响因子:
4.9
通讯作者:
HANCOCK, REW
HANCOCK, REW
中科院分区:
医学2区
文献类型:
--
作者:
ANGUS, BL;CAREY, AM;HANCOCK, REW

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铜绿假单胞菌突变体Z61对广泛的抗生素高度超敏感,包括β-内酰胺类、氨基糖苷类、利福平、四环素和氯霉素。使用庆大霉素或羧苄青霉素作为选择剂分离自发回复突变体,并显示对一组12种抗生素具有2种敏感性模式。部分回复突变体对这些抗生素的耐药性比突变体Z61高2- 10倍,而完全回复突变体的抗生素敏感性与突变体Z61所来源的野生型菌株K799的抗生素敏感性没有区别。生色β的摄取-在所有菌株的未诱导和诱导的细胞中,通过测量由诱导的周质β-内酰胺头孢菌素水解的稳态速率,研究了内酰胺头孢菌素。完整和破碎细胞中的内酰胺酶。这表明,在系列突变体Z61、部分回复突变体、野生型和完全回复突变体中,外膜通透性随着抗生素抗性的增加而降低。数据与低外膜渗透性是由外膜中低比例的开放功能性孔蛋白引起的想法一致,这是野生型铜绿假单胞菌菌株的高天然抗生素抗性的原因。低于突变体Z61的最小抑制浓度的苄青霉素水平不能诱导β-内酰胺酶产生。这是与所观察到的外膜渗透性增加的可能性进行了讨论。初步证据表明,孔形成的外膜孔蛋白F在突变体Z61中没有改变。
The P. aeruginosa mutant Z61 is highly supersusceptible to a wide range of antibiotics, including .beta.-lactams, aminoglycosides, rifampin, tetracycline and chloramphenicol. Spontaneous revertants were isolated, using gentamicin or carbenicillin as selective agents, and shown to have 2 patterns of susceptibility to a group of 12 antibiotics. Partial revertants had 2- to 10-fold greater resistance to these antibiotics than mutant Z61, whereas full revertants had antibiotic susceptibilities indistinguishable from those of the wild-type strain K799, from which mutant Z61 was derived. Uptake of a chromogenic .beta.-lactam nitrocefin was studied in both uninduced and induced cells of all strains by measuring the steady-state rate of nitrocefin hydrolysis by the inducible, periplasmic .beta.-lactamase in whole and broken cells. This demonstrated that outer membrane permeability decreased as antibiotic resistance increased in the series mutant Z61, partial revertants, wild type and full revertants. The data were consistent with the idea of low outer membrane permeability being caused by a low proportion of open functional porins in the outer membrane as the reason for the high natural antibiotic resistance of wild-type P. aeruginosa strains. Levels of benzylpenicillin below the minimal inhibitory concentration for mutant Z61 failed to induce .beta.-lactamase production. The possibility that this was related to the observed increase in outer membrane permeability is discussed. Preliminary evidence is presented that the pore-forming outer membrane porin protein F is not altered in mutant Z61.