Plotkin Balbina, Konaklieva Monika
Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515.
Department of Chemistry, American University, College of Arts and Sciences, 4400 Massachusetts Ave, NW, Washington, DC 20016.
ADMET DMPK. 2022 Jan 7;10(2):153-162. doi: 10.5599/admet.1164. eCollection 2022.
An obstacle to drug development, particularly in this era of multiple drug resistance, is the under-appreciation for the role the host environment plays in microbial response to drugs. With the rise in fungal infection and drug resistance, particularly in individuals with co-morbidities, the influence serum and its components have on antimicrobial susceptibility requires assessment. This study examined the impact of physiologically relevant glucose and insulin levels in the presence and absence of 50 % human plasma on MICs for clinical isolates of and . The addition of insulin or glucose at physiologic levels in RPMI medium alone altered the MIC in either a positive or negative fashion, depending on the organisms and drug tested, with most significantly altered with a 40, >32- and 46-fold increase in MIC for amphotericin B, itraconazole and miconazole, respectively. The addition of candida-antibody negative plasma also affected MIC, with the addition of glucose and insulin having a tandem effect on MIC. These findings indicate that phenotypic resistance of and can vary depending on the presence of insulin with glucose and plasma. This modulation of resistance may help explain treatment failures in the diabetic population and facilitate the development of stable drug-resistant strains. Furthermore, these findings indicate the need for a precision approach in the choice of drug treatment and drug development.
药物研发面临的一个障碍，尤其是在多重耐药性的这个时代，在于人们对宿主环境在微生物对药物反应中所起作用的认识不足。随着真菌感染及耐药性的增加，特别是在患有合并症的个体中，血清及其成分对抗菌药物敏感性的影响需要评估。本研究考察了在有和没有50%人血浆存在的情况下，生理相关的葡萄糖和胰岛素水平对白色念珠菌和热带念珠菌临床分离株最低抑菌浓度（MIC）的影响。仅在RPMI培养基中添加生理水平的胰岛素或葡萄糖，会根据所测试的微生物和药物，以正向或负向方式改变MIC，其中白色念珠菌受影响最为显著，两性霉素B、伊曲康唑和咪康唑的MIC分别显著增加40倍、>32倍和46倍。添加念珠菌抗体阴性血浆也会影响MIC，同时添加葡萄糖和胰岛素对MIC有协同作用。这些发现表明，白色念珠菌和热带念珠菌的表型耐药性可能因胰岛素与葡萄糖及血浆的存在而有所不同。这种耐药性的调节可能有助于解释糖尿病患者的治疗失败情况，并促进稳定耐药菌株的产生。此外，这些发现表明在药物治疗选择和药物研发中需要采用精准方法。
