Chandler C J, Segel I H
Antimicrob Agents Chemother. 1978 Jul;14(1):60-8. doi: 10.1128/AAC.14.1.60.
Pyrithione is a general inhibitor of membrane transport processes in fungi. A brief preincubation of Penicillium mycelia with pyrithione resulted in a marked decrease in the activities of a variety of independently regulated transport systems, including those for inorganic sulfate, inorganic phosphate, methylamine (actually, the NH(4) (+) permease), choline-O-sulfate, glucose, l-methionine (a specific system), and several hydrophobic l-alpha-amino acids (the general amino acid permease). The degree of inhibition at any fixed pyrithione concentration and exposure time increased as the pH of the incubation medium was decreased. This result strongly suggests that the active species is the un-ionized molecule and that pyrithione acts by collapsing a transmembrane DeltapH driving force. The degree of transport inhibition caused by a given concentration of pyrithione increased with increasing time of exposure to the inhibitor. However, exposure time and pyrithione concentration were not reciprocally related. At "low" pyrithione concentrations, transport inhibition plateaued at some finite value. This observation suggests that the fungi can detoxify low levels of the inhibitor. The concentration of pyrithione required for a given degree of growth inhibition increased as the experimental mycelial density increased. This phenomenon was consistent with the suggestion that the fungi are capable of inactivating pyrithione.
吡啶硫酮是真菌膜转运过程的一种通用抑制剂。用吡啶硫酮对青霉菌丝体进行短暂预孵育后，多种独立调节的转运系统的活性显著降低，包括无机硫酸盐、无机磷酸盐、甲胺（实际上是NH₄⁺通透酶）、硫酸胆碱-O、葡萄糖、L-甲硫氨酸（一种特定系统）以及几种疏水性L-α-氨基酸（通用氨基酸通透酶）的转运系统。在任何固定的吡啶硫酮浓度和暴露时间下，随着孵育培养基pH值的降低，抑制程度增加。这一结果强烈表明活性物质是未电离的分子，并且吡啶硫酮通过破坏跨膜的ΔpH驱动力起作用。给定浓度的吡啶硫酮引起的转运抑制程度随着暴露于抑制剂的时间增加而增加。然而，暴露时间和吡啶硫酮浓度并非呈反比关系。在“低”吡啶硫酮浓度下，转运抑制在某个有限值处达到平稳。这一观察结果表明真菌能够对低水平的抑制剂进行解毒。随着实验菌丝体密度的增加，给定程度的生长抑制所需的吡啶硫酮浓度增加。这一现象与真菌能够使吡啶硫酮失活的观点一致。
