A mechanistical model for the uptake of sulfonamides by bacteria.
A mechanistical model for the uptake of sulfonamides by bacteria.
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DOI：
10.1016/j.chemosphere.2007.07.045
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发表时间：
2008
期刊：
影响因子：
8.8
通讯作者：
C. Zarfl;M. Matthies;J. Klasmeier
中科院分区：
文献类型：
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作者：
C. Zarfl;M. Matthies;J. Klasmeier
用动态模型模拟了磺胺类药物在细菌细胞中的摄取过程，以评估磺胺类药物在细菌细胞中的生物利用度和稳态累积。磺胺类药物的吸收被模拟为中性分子和离子物种的类扩散传输。胞外和胞内的形态取决于胞外和胞内的pH值以及抗生素活性SO2NH部分的pKa值。细胞内和细胞外磺胺浓度的比率被用来衡量磺胺在细菌细胞中的潜在积累。PKa2值在5.0~11.8之间的各种磺胺类化合物的模拟比与实验数据吻合较好。敏感性分析表明，胞内磺胺浓度显著依赖于细胞质和周围介质中的电离程度。如果外部pH超过细胞内pH，细胞内不会发生蓄积。对于pKa值较大的磺胺类化合物，其内部活性等于胞外溶液中的活性。从细胞内到细胞外的pH梯度较大时，细菌的积累最大，这取决于细菌的pH调节机制。各种磺胺类药物依赖于pH的细胞内积累与它们对选定细菌的观察到的抗生素作用有很好的相关性。
The uptake of sulfonamides into bacterial cells was simulated by a dynamic model to estimate bioavailability and steady-state accumulation of sulfonamides in the cells. Uptake of sulfonamides is modeled as diffusion-like transport of the neutral molecule and the ionic species. Speciation outside and inside the cell depends on the extra- and intracellular pH and the pKa-value of the antibiotic active SO2NH moiety. The ratio between intra- and extracellular sulfonamide concentration is used as a measure for potential sulfonamide accumulation in bacterial cells. Simulated ratios are in good agreement with experimental data for various sulfonamides with pKa2values ranging from 5.0 up to 11.8. Sensitivity analyses indicate that intracellular sulfonamide concentration depend significantly on the degree of ionization in the cytoplasm and the surrounding medium. No accumulation in the cell occurs, if the external pH exceeds the intracellular pH. For sulfonamides with large pKa-values the internal activity equals the activity in the extracellular solution. Highest accumulation is reached if the pH gradient from inside to outside the cell is large, which depends on the bacterial pH-regulation mechanisms. The pH-dependent intracellular accumulation of various sulfonamides correlates well with their observed antibiotic effect on selected bacteria.