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新型抗生素对抗抗药性肺结核

来源:生物谷 2014-07-04 15:34

2014年7月4讯 /生物谷BIOON/ --随着抗药性肺结核在世界范围内的传播,人们对抗这种疾病的手段变得越来越少。不过最近研究人员通过对一种经典抗生素24-desmethylrifampicin进行修饰得到了一种治疗肺结核效果甚好的潜在药物。

一般来说,医学工作者将治疗肺结核药物分为三等,一线药物能够在绝大多数情况下起到治疗效果,如利福平;当一线药物无法起作用时,如病原体对这些药物产生较强抗药性时,就采用二线药物乃至三线药物。但是这些药物并不十分理想。

利福平和相关药物是重要的抗生素,每年全世界有超过100万人死于肺结核,是在艾滋病之后,传染病死亡的第二个最常见的原因。俄勒冈州立大学Taifo Mahmud表示:我们相信这些发现对治疗多耐药结核病是重要的。

当细菌RNA聚合酶发生变异时,利福平和相关抗生素的耐药性发生,Mahmud说:变异使得细菌基本上不受抗生素(通过抑制RNA的合成来发挥工作)影响。研究人员修改药物,使得它可以有效地绑定到这个变异型酶,再次实现了其有效性。(生物谷Bioon.com)

详细英文报道:

As cases of drug-resistant tuberculosis rise worldwide, doctors have fewer effective options with which to treat patients. But scientists have successfully modified the precursor to one of the common antibacterial drugs used to treat tuberculosis, an important step toward developing new therapies that can treat this growing global health concern.

Researchers at Oregon State University, along with collaborators from the University of Delhi and the Institute of Genomics and Integrative Biology in India, have designed a new compound, 24-desmethylrifampicin, to have better antibacterial activity than rifampicin, a first-line drug used to treat tuberculosis and other infections. The findings are reported in The Journal of Biological Chemistry.

First-line drugs like rifampicin and others are the most effective drugs against tuberculosis. Some patients are resistant to first-line drugs, in which case, second-line drugs are necessary. Third-line drugs are used in rare cases and they may not be useful.

Rifampicin is often used alongside other drugs in a cocktail therapy that takes about six months of treatment to cure tuberculosis. But multi-drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have become resistant to rifampicin and can take 18 months to several years to treat.

Drug resistance in rifampicin and related antibiotics occurs when the bacterial RNA polymerase enzymes mutate in the pathogen, explained Taifo Mahmud, a professor in the College of Pharmacy at Oregon State University and a corresponding author on the study, in a statement. When that happens, antibiotics that work by inhibiting RNA synthesis no longer work against the pathogen. But 24-desmethylrifampicin works by modifying the drug so it can effectively bind to this mutated enzyme and once again be effective.

"We found out how the antibiotic-producing bacteria make this compound, and then genetically modified that system to remove one part of the backbone of the molecule," Mahmud said. "Understanding this whole process should allow us to create not just this one, but a range of different analogs that can be tested for their efficacy as new antibiotics."

This new approach could help generate more analogs of rifamycin--the class of drugs rifampicin belongs to--to combat the threat of drug-resistant strains of tuberculosis, according to the investigators.

 

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