研究显示,维生素C能杀死抗药性的结核分枝杆菌

Scientists at the Albert Einstein College of Medicine in New York have unexpectedly discovered that vitamin C can kill drug-resistant tuberculosis bacteria.

 

纽约爱因斯坦医学院的科学家出人意料地发现,维生素C可以杀死抗药性肺结核细菌。

这个扫描电子显微图显示了一些结核分枝杆菌的细胞壁结构中所见的超微结构细节(Janice Haney Carr)

 

 

发表在《自然通讯》(Nature Communications)杂志上的这一研究结果表明,添加到现有抗结核药物中的维生素C可以缩短治疗时间,并突出一个新的药物设计领域。

 

肺结核是由结核分枝杆菌感染引起的。世界卫生组织(World Health Organization)的数据显示,在低收入和中等收入国家,这一疾病尤为严重, 超过这些国家的结核相关死亡人数的95%

 

未能对抗结核药物作出反应的感染是一个日益严重的问题:全世界约有65万人患有耐多种药物的结核病,其中9%的人患有广泛耐药肺结核病。

 

这一发现是在研究结核病细菌如何对异烟肼(一种有效的一线抗结核药物)产生耐药性的研究中发现的。

 

科学家们观察到,异烟肼耐药结核菌在一种名为mycothiol的分子中存在缺陷。

“我们假设结核菌不能使霉菌含有更多的半胱氨酸,一种氨基酸,”资深作家William Jacobs教授解释说。

 

因此,我们预测如果我们在培养中加入异烟肼和半胱氨酸对异烟肼敏感的结核分枝杆菌,细菌就会产生耐药性。相反,我们最终扼杀了培养物——完全出乎意料的事情。”

 

研究小组怀疑,半胱氨酸可以作为一种还原剂来帮助杀死结核菌,从而引发活性氧的产生,从而破坏DNA

 

维生素C对结核分枝杆菌的作用: 维生素C进入结核分枝杆菌细胞,减少铁离子产生亚铁离子,在存在氧的情况下,产生过氧化氢、过氧化氢和羟自由基;这些活性氧的产生会导致DNA损伤、脂质改变和氧化还原平衡(Catherine Vilcheze等人)

 

维生素C对结核分枝杆菌的作用:维生素C进入结核分枝杆菌细胞,减少铁离子产生亚铁离子,在存在氧的情况下,产生过氧化氢、过氧化氢和羟自由基; 这些活性氧的产生会导致DNA损伤、脂质改变和氧化还原平衡(Catherine Vilcheze等人)。

 

 

 

为了验证这一假设,我们使用异烟肼和一种不同的还原剂——维生素C重复了实验。异烟肼和维生素C的结合对结核分枝杆菌的培养进行了灭菌。随后,我们惊讶地发现,维生素C本身不仅对药物敏感的结核病进行了消毒,而且还消除了耐多种药的结核病和广泛耐药菌株。

 

为了证明在临床试验中检测维生素C的合理性,研究小组需要找到维生素C发挥其致命作用的分子机制。

 

更多的研究产生了答案——维生素C引发了所谓的芬顿反应(Fenton反应),导致铁与其他分子发生反应,产生活性氧,杀死结核杆菌。

 

“我们不知道维生素C是否能在人体内发挥作用,但我们现在有了进行临床试验的合理基础。它也有助于我们了解维生素C是便宜的,广泛使用并且非常安全的使用。至少,这项工作向我们展示了一种新的机制,我们可以利用它来攻击结核病。雅各布斯教授总结道。

 

 

 

参考文献

Scientists at the Albert Einstein College of Medicine in New York have unexpectedly discovered that vitamin C can kill drug-resistant tuberculosis bacteria.

 

This scanning electron micrograph shows some of the ultrastructural details seen in the cell wall configuration of a number of Mycobacterium tuberculosis bacteria (Janice Haney Carr)

This scanning electron micrograph shows some of the ultrastructural details seen in the cell wall configuration of a number of Mycobacterium tuberculosis bacteria (Janice Haney Carr)

The findings, published in the journal Nature Communications, suggest that vitamin C added to existing anti-tuberculosis drugs could shorten therapy, and highlight a new area for drug design.

 

Tuberculosis is caused by infection with the bacterium Mycobacterium tuberculosis. The disease is especially acute in low and middle income countries, which account for more than 95 percent of tuberculosis-related deaths, according to the World Health Organization.

 

Infections that fail to respond to anti-tuberculosis drugs are a growing problem: about 650,000 people worldwide now have multi-drug-resistant tuberculosis, 9 percent of whom have extensively drug-resistant tuberculosis.

 

The discovery arose during research into how tuberculosis bacteria become resistant to isoniazid, a potent first-line anti-tuberculosis drug.

 

The scientists observed that isoniazid-resistant tuberculosis bacteria were deficient in a molecule called mycothiol.

 

We hypothesized that tuberculosis bacteria that can’t make mycothiol might contain more cysteine, an amino acid,” explained senior author Prof William Jacobs.

 

So, we predicted that if we added isoniazid and cysteine to isoniazid-sensitive Mycobacterium tuberculosis in culture, the bacteria would develop resistance. Instead, we ended up killing off the culture – something totally unexpected.”

 

The team suspected that cysteine was helping to kill tuberculosis bacteria by acting as a reducing agent that triggers the production of reactive oxygen species, which can damage DNA.

 

Action of vitamin C against Mycobacterium tuberculosis: vitamin C enters Mycobacterium tuberculosis cells and reduces ferric ions to generate ferrous ions that, in presence of oxygen, will produce superoxide, hydrogen peroxide and hydroxyl radicals; the production of these reactive oxygen species leads to the DNA damage, alteration of lipids and redox balance (Catherine Vilchèze et al)

Action of vitamin C against Mycobacterium tuberculosis: vitamin C enters Mycobacterium tuberculosis cells and reduces ferric ions to generate ferrous ions that, in presence of oxygen, will produce superoxide, hydrogen peroxide and hydroxyl radicals; the production of these reactive oxygen species leads to the DNA damage, alteration of lipids and redox balance (Catherine Vilchèze et al)

To test this hypothesis, we repeated the experiment using isoniazid and a different reducing agent – vitamin C. The combination of isoniazid and vitamin C sterilized the Mycobacterium tuberculosis culture. We were then amazed to discover that vitamin C by itself not only sterilized the drug-susceptible tuberculosis, but also sterilized multi-drug-resistant tuberculosis and extensively drug-resistant strains,” Prof Jacobs said.

 

To justify testing vitamin C in a clinical trial, the team needed to find the molecular mechanism by which vitamin C exerted its lethal effect.

 

More research produced the answer – vitamin C induced what is known as a Fenton reaction, causing iron to react with other molecules to create reactive oxygen species that kill the tuberculosis bacteria.

 

We don’t know whether vitamin C will work in humans, but we now have a rational basis for doing a clinical trial. It also helps that we know vitamin C is inexpensive, widely available and very safe to use. At the very least, this work shows us a new mechanism that we can exploit to attack tuberculosis,” Prof Jacobs concluded.

 

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Bibliographic information: Catherine Vilchèze et al. 2013. Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction. Nature Communications 4, article number: 1881; doi: 10.1038/ncomms2898

 

Vitamin C Kills Drug-Resistant Mycobacterium tuberculosis, Study Shows | Medicine | Sci-News.com  http://www.sci-news.com/medicine/article01093-vitamin-c-mycobacterium-tuberculosis.html