Bartzatt R, Benish T, Koziol K, Stoddard J
University of Nebraska, Chemistry Department, College of Arts and Sciences Omaha, Nebraska 68182-0109, USA.
Physiol Chem Phys Med NMR. 2000;32(1):49-56; discussion 56.
Bacterial resistance to antibiotics is a significant problem in health facilities and results in higher costs for health care and increased fatalities due to infection. The work presented here suggests that antibiotic molecular structure can be altered in a selected manner, which will revive the bacterial growth inhibiting capability. A bacterial strain PKK3535(DH1), which is resistant to the antibiotic ampicillin, was found to be highly growth inhibited by these altered forms of ampicillin when tested in tissue culture. The level of growth inhibition of bacterial strain PKK3535(DHI) was greater than 50%, for both molecular variants of ampicillin that were investigated. The bacteria strain used for testing was a clinical isolate obtained from the University Hospital of the University of Nebraska, Omaha. These two antibiotic variants were methylated ampicillin and ethylated ampicillin. The synthetic procedure for generating these variants is presented as well as the molecular structure. The methylated and ethylated ampicillin were found to be stable at 0 degrees C for many weeks, were somewhat less soluble than normal ampicillin, but dissolved in LB plate media. The resistant bacteria strain was plated onto LB media with altered ampicillin and profound inhibition of bacteria growth was seen within the first 24 hours of incubation. These molecular variants of ampicillin provide evidence of a means to combat the proliferation of resistant bacterial strains. The molecular alteration of antibiotics may provide a suitable means to study and combat the appearance of antibiotic-resistant bacteria.
细菌对抗生素的耐药性是医疗机构中一个严重的问题，会导致医疗成本增加以及因感染造成的死亡人数上升。本文所展示的研究表明，可以以特定方式改变抗生素的分子结构，从而恢复其抑制细菌生长的能力。在组织培养试验中发现，对氨苄青霉素具有耐药性的细菌菌株PKK3535（DH1），会受到这些氨苄青霉素变体的高度生长抑制。对于所研究的两种氨苄青霉素分子变体，细菌菌株PKK3535（DHI）的生长抑制水平均超过50%。用于测试的细菌菌株是从奥马哈内布拉斯加大学大学医院获取的临床分离株。这两种抗生素变体分别是甲基化氨苄青霉素和乙基化氨苄青霉素。文中介绍了生成这些变体的合成方法以及分子结构。甲基化和乙基化氨苄青霉素在0摄氏度下可稳定保存数周，其溶解度略低于普通氨苄青霉素，但可溶解于LB平板培养基中。将耐药细菌菌株接种到含有变体氨苄青霉素的LB培养基上，在培养的最初24小时内即可观察到细菌生长受到显著抑制。这些氨苄青霉素分子变体为对抗耐药细菌菌株的增殖提供了一种方法的证据。抗生素的分子改变可能为研究和对抗抗生素耐药细菌的出现提供一种合适的手段。
