Diphenyleneiodonium chloride (DPIC) displays broad-spectrum bactericidal activity.
Diphenyleneiodonium chloride (DPIC) displays broad-spectrum bactericidal activity.
复制标题
DOI：
10.1038/s41598-017-11575-5
复制
发表时间：
2017-09-14
影响因子：
4.6
通讯作者：
Pandey AK
中科院分区：
文献类型：
--
作者：
Pandey M;Singh AK;Thakare R;Talwar S;Karaulia P;Dasgupta A;Chopra S;Pandey AK
抗生素在全球范围内的滥用已导致耐药病原体在医院以及更令人担忧的社区环境中的出现增加。此外，公司兴趣和财务承诺的减少对迅速减少的抗微生物药物发现和开发计划施加了越来越大的压力。在此背景下，我们筛选了药理学活性化合物文库（LOPAC，Sigma）以对抗金黄色葡萄球菌和结核分枝杆菌，从而在非抗生素分子中鉴定有效的新型抗微生物分子。进行基于微孔板的全细胞生长测定以分析化合物对金黄色葡萄球菌和结核分枝杆菌的抗微生物效力。我们确定了氯化二苯碘铵，一种有效的NADH/NADPH氧化酶抑制剂，作为一种广谱抗生素，对金黄色葡萄球菌和结核分枝杆菌的耐药菌株有效。有趣的是，氯化二苯碘铵对生长缓慢的非复制型结核杆菌持留菌也非常有效。FIC指数表明，氯化二苯碘鎓与利福平之间存在强烈的协同作用，而与INH之间不存在相互作用。在体内小鼠前列腺素缺乏症大腿S中进一步验证了氯化二苯碘铵的抗菌特性。金黄色葡萄球菌感染模型。综上所述，这些发现表明，氯化二苯碘铵可能被重新用于治疗结核病和葡萄球菌感染。
Indiscriminate use of antibiotics globally has lead to an increase in emergence of drug-resistant pathogens under both nosocomial, as well as more worryingly, in community setting as well. Further, a decrease in the corporate interest and financial commitment has exerted increasing pressure on a rapidly dwindling antimicrobial drug discovery and developmental program. In this context, we have screened the Library of Pharmacologically Active Compounds (LOPAC, Sigma) against Staphylococcus aureus and Mycobacterium tuberculosis to identify potent novel antimicrobial molecules amongst non-antibiotic molecules. Microplate-based whole cell growth assay was performed to analyze the antimicrobial potency of the compounds against Staphylococcus aureus and Mycobacterium tuberculosis. We identified diphenyleneiodonium chloride, a potent inhibitor of NADH/NADPH oxidase, as a broad-spectrum antibiotic potently active against drug resistant strains of Staphylococcus aureus and Mycobacterium tuberculosis. Intriguingly, the diphenyleneiodonium chloride was also very effective against slow-growing non-replicating Mtb persisters. FIC index demonstrated a strongly synergistic interaction between diphenyleneiodonium chloride and Rifampicin while it did not interact with INH. The antimicrobial property of the diphenyleneiodonium chloride was further validated in vivo murine neutropenic thigh S. aureus infection model. Taken together, these findings suggest that Diphenyleneiodonium chloride can be potentially repurposed for the treatment of tuberculosis and staphylococcal infections.
登录
查看更多内容
结核病药物治疗：优化患者护理的策略。
影响因子：
3.2
作者：
通讯作者：
--
影响因子：
4.6
作者：
Aljayyoussi G;Jenkins VA;Sharma R;Ardrey A;Donnellan S;Ward SA;Biagini GA
通讯作者：
Biagini GA
影响因子：
30.3
作者：
Cohen NR;Lobritz MA;Collins JJ
通讯作者：
Collins JJ
影响因子：
11.8
作者：
Nahid, Payam;Dorman, Susan E.;Vernon, Andrew
通讯作者：
Vernon, Andrew
利福平在药物相互作用中的作用：涉及核孕烷 X 受体的潜在分子机制。
影响因子：
5.7
作者：
Chen, Jiezhong;Raymond, Kenneth
通讯作者：
Raymond, Kenneth