INVALIDITY FOR PSEUDOMONAS-AERUGINOSA OF AN ACCEPTED MODEL OF BACTERIAL PERMEABILITY TO BETA-LACTAM ANTIBIOTICS
INVALIDITY FOR PSEUDOMONAS-AERUGINOSA OF AN ACCEPTED MODEL OF BACTERIAL PERMEABILITY TO BETA-LACTAM ANTIBIOTICS
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DOI：
10.1128/aac.35.5.916
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发表时间：
1991-05-01
影响因子：
4.9
通讯作者：
DAVY, KWM
中科院分区：
文献类型：
--
作者：
LIVERMORE, DM;DAVY, KWM
β-内酰胺抗生素渗透到革兰氏阴性菌中的公认模型是由Zimmermann和Rosselet（Antimicrob.探员Chemother 12：368-372，1977）。 该模型假设（i）抗生素分子穿过外膜的扩散遵守菲克定律，并且可以通过生物体和药物的任何给定组合的渗透常数来表征，（ii）周质内的药物水解遵守Michaelis-Menten动力学，以及（iii）在药物摄取和水解之间快速达到稳态。 该模型允许从大肠杆菌菌株的β-内酰胺酶生产和渗透性特征的知识中准确预测抗生素MIC。 有人建议，该模型是不合适的铜绿假单胞菌，但试图确认这已被困扰的实验困难，估计该物种的渗透系数。 在本研究中，我们测试了该模型的预测，即含有质粒编码的β-内酰胺酶的铜绿假单胞菌transconjugants的总体耐药性应继续部分取决于渗透性。 PSE-4 β-内酰胺酶的接合转移体在具有广泛不同水平的内在耐药性的宿主菌株中构建，可能是不透性决定的耐药性。 与模型的预测相反，所有的transconjugants开发相同的总体水平的耐药性底物β-内酰胺类药物，如阿洛西林和头孢哌酮，无论初始水平的内在耐药性的受体菌株。 我们的结论是，该模型是不合适的铜绿假单胞菌，并讨论了可能的解释生物体的行为。
The accepted model for the penetration of beta-lactam antibiotics into gram-negative bacteria is that proposed by Zimmermann and Rosselet (Antimicrob. Agents Chemother. 12:368-372, 1977). The model assumes (i) that diffusion of the antibiotic molecules across the outer membrane obeys Fick's law and can be characterized by a permeability constant for any given combination of organism and drug, (ii) that drug hydrolysis within the periplasm obeys Michaelis-Menten kinetics, and (iii) that a steady state is rapidly attained between drug uptake and hydrolysis. The model has allowed accurate prediction of antibiotic MICs for Escherichia coli strains from a knowledge of their beta-lactamase production and permeability characteristics. It has been suggested that the model is inappropriate for Pseudomonas aeruginosa, but attempts to confirm this have been bedevilled by experimental difficulties in estimating permeability coefficients for this species. In the present study, we tested a prediction of the model that the overall resistance of P. aeruginosa transconjugants containing a plasmid-encoded beta-lactamase should continue to depend partly on permeability. Transconjugants with PSE-4 beta-lactamase were constructed in host strains with widely different levels of intrinsic, presumably impermeability-determined resistance. Contrary to the prediction of the model, all the transconjugants developed identical overall levels of resistance to substrate beta-lactams, such as azlocillin and cefoperazone, irrespective of the initial levels of intrinsic resistance of the recipient strains. We conclude that the model is inappropriate for P. aeruginosa, and possible explanations for the organism's behavior are discussed.